title: Twins with progressive thoracic aortic aneurysm, recurrent dissection and ACTA2 mutation.
abstract: 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.
authors.affiliation: Division of Human Genetics, and Division of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio stware@iu.edu.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Ware
authors.affiliation: Division of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Amy
authors.initials: A
authors.lastname: Shikany
authors.affiliation: Division of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Landis
authors.affiliation: Division of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Jeanne F
authors.initials: JF
authors.lastname: James
authors.affiliation: Division of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Hinton
mesh_terms: D000199:Actins / Q000235:genetics*; D000293:Adolescent; D000784:Aortic Dissection / Q000175:diagnosis / Q000235:genetics*; D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis / Q000235:genetics*; D018450:Disease Progression; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D012008:Recurrence; D014427:Twins / Q000235:genetics*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins
keywords: ACTA2; aortic aneurysm; aortopathy; genetics; mydriasis; natural history