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Thoracic aortic disease in two patients with juvenile polyposis syndrome and SMAD4 mutations

Authors

  • Polakit Teekakirikul,

    1. Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts
    2. Department of Genetics, Harvard Medical School and Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts
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  • Dianna M. Milewicz,

    1. Division of Medical Genetics, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas
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  • David T. Miller,

    1. Harvard Medical School, Boston, Massachusetts
    2. Division of Genetics and Department of Laboratory Medicine, Children's Hospital Boston, Boston, Massachusetts
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  • Ronald V. Lacro,

    1. Harvard Medical School, Boston, Massachusetts
    2. Department of Cardiology, Children's Hospital Boston, Boston, Massachusetts
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  • Ellen S. Regalado,

    1. Division of Medical Genetics, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas
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  • Ana Maria Rosales,

    1. Harvard Medical School, Boston, Massachusetts
    2. Pediatric Cardiology Unit, MassGeneral Hospital for Children, Boston, Massachusetts
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  • Daniel P. Ryan,

    1. Harvard Medical School, Boston, Massachusetts
    2. Department of Pediatric Surgery, MassGeneral Hospital for Children, Boston, Massachusetts
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  • Tomi L. Toler,

    1. Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts
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  • Angela E. Lin M.D.

    Corresponding author
    1. Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts
    2. Harvard Medical School, Boston, Massachusetts
    • Medical Genetics, MassGeneral Hospital for Children, 185 Cambridge Street, CPZN-2222, Boston, MA 02114.
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  • How to Cite this Article: Teekakirikul P, Milewicz DM, Miller DT, Lacro RV, Regalado ES, Rosales AM, Ryan DP, Toler TL, Lin AE. 2012. Thoracic aortic disease in two patients with juvenile polyposis syndrome and SMAD4 mutations. Am J Med Genet Part A 161A:185–191.

  • Conflict of interest: The authors declare no conflict of interest.

Abstract

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 (TGFBR1, TGFBR2, FBN1, and SMAD3) cause syndromic and inherited TAAD. SMAD4 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 SMAD4 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 SMAD4 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 SMAD4 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 SMAD4 mutations. We propose that the thoracic aorta should be screened in patients with SMAD4 mutations to prevent untimely death from dissection. This report also confirms that SMAD4 mutations predispose to TAAD. © 2012 Wiley Periodicals, Inc.

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