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.
Article first published online: 13 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 1, pages 185–191, January 2013
How to Cite
Teekakirikul, P., Milewicz, D. M., Miller, D. T., Lacro, R. V., Regalado, E. S., Rosales, A. M., Ryan, D. P., Toler, T. L. and Lin, A. E. (2013), Thoracic aortic disease in two patients with juvenile polyposis syndrome and SMAD4 mutations. Am. J. Med. Genet., 161: 185–191. doi: 10.1002/ajmg.a.35659
Conflict of interest: The authors declare no conflict of interest.
- Issue published online: 22 DEC 2012
- Article first published online: 13 DEC 2012
- Manuscript Accepted: 22 AUG 2012
- Manuscript Received: 19 FEB 2012
- Unknown funding agency. Grant Numbers: P50HL083794-01, RO1 HL62594
- aortic dilation;
- hereditary hemorrhagic telangiectasia;
- juvenile polyposis syndrome;
- TGF-beta signaling;
- thoracic aortic aneurysm and dissection
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.