{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T15:05:05Z","timestamp":1774969505186,"version":"3.50.1"},"reference-count":19,"publisher":"American Academy of Pediatrics (AAP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:p>Thoracic aortic aneurysm (TAA) is a genetically mediated disease with variable age of onset. In the pediatric age range, nonsyndromic TAA frequently has a milder course than syndromic forms of TAA, such as Marfan syndrome or Loeys-Dietz syndrome. Herein, we describe 17-year-old identical twin brothers with severe progressive TAA due to a novel de novo ACTA2 mutation. Interestingly, both boys were diagnosed at age 11 with congenital mydriasis, a recently recognized manifestation of some ACTA2 mutations due to smooth muscle dysfunction. One of the brothers presented with acute-onset lower back pain that was identified as dissection of an abdominal aortic aneurysm. Imaging of the chest at this time showed severe fusiform TAA. Cardiac imaging in his twin showed similar TAA, but no abdominal aortic aneurysm. Both brothers underwent valve-sparing aortic root replacement, but have had progressive aortic disease with recurrent dissection requiring multiple surgeries. This case emphasizes the importance of identifying physical stigmata of smooth muscle dysfunction, such as mydriasis, as potential markers for associated aortopathy and vascular diseases.<\/jats:p>","DOI":"10.1542\/peds.2013-2503","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T04:36:33Z","timestamp":1410842193000},"page":"e1218-e1223","source":"Crossref","is-referenced-by-count":15,"title":["Twins With Progressive Thoracic Aortic Aneurysm, Recurrent Dissection and<i>ACTA2<\/i>Mutation"],"prefix":"10.1542","volume":"134","author":[{"given":"Stephanie M.","family":"Ware","sequence":"first","affiliation":[{"name":"Division of Human Genetics, and"},{"name":"Division of Cardiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Shikany","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin J.","family":"Landis","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanne F.","family":"James","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert B.","family":"Hinton","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2014,10,1]]},"reference":[{"issue":"7347","key":"2021120903443060400_B1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/nature10145","article-title":"Lessons on the pathogenesis of aneurysm from heritable conditions.","volume":"473","author":"Lindsay","year":"2011","journal-title":"Nature"},{"key":"2021120903443060400_B2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1146\/annurev.genom.8.080706.092303","article-title":"Genetic basis of thoracic aortic aneurysms and dissections: focus on smooth muscle cell contractile dysfunction.","volume":"9","author":"Milewicz","year":"2008","journal-title":"Annu Rev Genomics Hum Genet"},{"issue":"2","key":"2021120903443060400_B3","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.ijcard.2011.08.079","article-title":"Novel MYH11 and ACTA2 mutations reveal a role for enhanced TGF\u03b2 signaling in FTAAD.","volume":"165","author":"Renard","year":"2013","journal-title":"Int J Cardiol"},{"issue":"12","key":"2021120903443060400_B4","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1038\/ng.2007.6","article-title":"Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.","volume":"39","author":"Guo","year":"2007","journal-title":"Nat Genet"},{"issue":"4","key":"2021120903443060400_B5","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1097\/GIM.0b013e3181cdd687","article-title":"Genetic variants promoting smooth muscle cell proliferation can result in diffuse and diverse vascular diseases: evidence for a hyperplastic vasculomyopathy.","volume":"12","author":"Milewicz","year":"2010","journal-title":"Genet Med"},{"issue":"pt 8","key":"2021120903443060400_B6","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1093\/brain\/aws172","article-title":"A novel distinctive cerebrovascular phenotype is associated with heterozygous Arg179 ACTA2 mutations.","volume":"135","author":"Munot","year":"2012","journal-title":"Brain"},{"issue":"4","key":"2021120903443060400_B7","first-page":"509","article-title":"Clinicopathologic reports, case reports, and small case series: congenital mydriasis, failure of accommodation, and patent ductus arteriosus.","volume":"120","author":"Gr\u00e4f","year":"2002","journal-title":"Arch Ophthalmol"},{"issue":"4","key":"2021120903443060400_B8","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/j.1600-0420.2005.00496.x","article-title":"Congenital mydriasis combined with aneurysmal dilatation of a persistent ductus arteriosus Botalli: a rare syndrome.","volume":"83","author":"Lindberg","year":"2005","journal-title":"Acta Ophthalmol Scand"},{"issue":"6","key":"2021120903443060400_B9","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1002\/ajmg.a.35858","article-title":"ACTA2 mutation with childhood cardiovascular, autonomic and brain anomalies and severe outcome.","volume":"161A","author":"Meuwissen","year":"2013","journal-title":"Am J Med Genet A"},{"issue":"4","key":"2021120903443060400_B10","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1177\/0883073812446631","article-title":"Neonatal stroke and progressive leukoencephalopathy in a child with an ACTA2 mutation.","volume":"28","author":"Moosa","year":"2013","journal-title":"J Child Neurol"},{"issue":"3","key":"2021120903443060400_B11","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/ajmg.a.35206","article-title":"R179H mutation in ACTA2 expanding the phenotype to include prune-belly sequence and skin manifestations.","volume":"158A","author":"Richer","year":"2012","journal-title":"Am J Med Genet A"},{"issue":"10","key":"2021120903443060400_B12","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1002\/ajmg.a.33657","article-title":"De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction.","volume":"152A","author":"Milewicz","year":"2010","journal-title":"Am J Med Genet A"},{"issue":"5","key":"2021120903443060400_B13","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.ajhg.2009.04.007","article-title":"Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.","volume":"84","author":"Guo","year":"2009","journal-title":"Am J Hum Genet"},{"issue":"13","key":"2021120903443060400_B14","doi-asserted-by":"crossref","first-page":"11356","DOI":"10.1074\/jbc.M110.203174","article-title":"Allele-specific effects of thoracic aortic aneurysm and dissection alpha-smooth muscle actin mutations on actin function.","volume":"286","author":"Bergeron","year":"2011","journal-title":"J Biol Chem"},{"issue":"13","key":"2021120903443060400_B15","doi-asserted-by":"crossref","first-page":"e266","DOI":"10.1161\/CIR.0b013e3181d47d48","article-title":"2010 ACCF\/AHA\/AATS\/ACR\/ASA\/SCA\/SCAI\/SIR\/STS\/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine.","volume":"121","author":"Hiratzka","year":"2010","journal-title":"Circulation"},{"issue":"3","key":"2021120903443060400_B16","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1161\/CIRCRESAHA.113.300675","article-title":"Genetics of thoracic aortic aneurysm: at the crossroad of transforming growth factor-\u03b2 signaling and vascular smooth muscle cell contractility.","volume":"113","author":"Gillis","year":"2013","journal-title":"Circ Res"},{"issue":"4","key":"2021120903443060400_B17","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.jacc.2003.08.054","article-title":"Characterizing the young patient with aortic dissection: results from the International Registry of Aortic Dissection (IRAD).","volume":"43","author":"Januzzi","year":"2004","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"2021120903443060400_B18","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.ahj.2008.10.005","article-title":"Rationale and design of the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC).","volume":"157","author":"Eagle","year":"2009","journal-title":"Am Heart J"},{"issue":"7","key":"2021120903443060400_B19","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1001\/jama.283.7.897","article-title":"The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease.","volume":"283","author":"Hagan","year":"2000","journal-title":"JAMA"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/134\/4\/e1218\/1099805\/peds_2013-2503.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/134\/4\/e1218\/1099805\/peds_2013-2503.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T16:58:28Z","timestamp":1746377908000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/134\/4\/e1218\/32963\/Twins-With-Progressive-Thoracic-Aortic-Aneurysm"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,1]]},"references-count":19,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2014,10,1]]},"published-print":{"date-parts":[[2014,10,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2013-2503","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,1]]}}}