title: Clinical and genetic characterization of adult patients presenting with non-syndromic vascular aneurysms and dissections.
abstract: BACKGROUND
  Genetic disorders affecting the arterial tree in the form of aneurysms and dissections are highly morbid conditions that strike younger persons leading to bleeding, infarction, or even death. Although clinically recognizable syndromes, notably Marfan, Ehlers Danlos, and Loeys-Dietz syndromes encompass the principal diagnosable phenotypes along the genetic vascular disorder spectrum, a substantial subset of patients cannot be adequately classified under a known diagnosis through clinical or molecular diagnostic methods. Here we describe patients presenting with multiple-aneurysms and/or pseudoaneurysm syndromes (MAPS), and clinically characterize this novel phenotype, present data on natural history and prognosis, and propose management guidelines.
  
  
  METHODS
  Thirty-two patients with MAPS were identified from February 2006 to October 2015 through the University of Colorado Adult Medical Genetics Clinic. A subset of patients underwent clinical genetic testing utilizing the Marfan/TAAD/Related disorders panel, and another subset was enrolled for research-based exome-sequencing.
  
  
  RESULTS
  Thirty-two patients (10 men, 22 women) were classified as MAPS patients with an average age of diagnosis at 39.5 (±13.3) and 35.4 (±12.8) years, respectively. Symptom presentation and progression are presented based on vascular territory, notably of the heart, head, and neck, which could manifest with fatal complications. Secondary arterial events occurred at an average of 6.7±6.0 years after the initial MAPS episode. Genetic analysis revealed 9 gene variants that are likely pathogenic and implicated in MAPS.
  
  
  CONCLUSIONS
  These data more broadly illuminate a phenotype of aneurysms, dissections, and/or pseudoaneurysms that do not classify under a recognizable genetic vascular diagnosis. Our data should provide useful clinical information for providers managing patients with MAPS.
authors.affiliation: Adult Medical Genetics Program and Division of Cardiology, University of Colorado Denver, Denver, CO, USA.|Department of Medicine, Reading Hospital, West Reading, PA, USA.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: D'Souza
authors.affiliation: Adult Medical Genetics Program and Division of Cardiology, University of Colorado Denver, Denver, CO, USA.
authors.forename: Dobromir
authors.initials: D
authors.lastname: Slavov
authors.affiliation: Adult Medical Genetics Program and Division of Cardiology, University of Colorado Denver, Denver, CO, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Graw
authors.affiliation: Adult Medical Genetics Program and Division of Cardiology, University of Colorado Denver, Denver, CO, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Jirikowic
authors.affiliation: Adult Medical Genetics Program and Division of Cardiology, University of Colorado Denver, Denver, CO, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Todd
authors.affiliation: Adult Medical Genetics Program and Division of Cardiology, University of Colorado Denver, Denver, CO, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Rogers
authors.affiliation: Adult Medical Genetics Program and Division of Cardiology, University of Colorado Denver, Denver, CO, USA - matthew.taylor@ucdenver.edu.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Taylor
mesh_terms: D000328:Adult; D000784:Aortic Dissection / Q000000981:diagnostic imaging / Q000235:genetics*; D017541:Aneurysm, False / Q000000981:diagnostic imaging; D017545:Aortic Aneurysm, Thoracic / Q000000981:diagnostic imaging / Q000235:genetics*; D003120:Colorado; D000072226:Computed Tomography Angiography; D005260:Female; D006257:Head / Q000000981:diagnostic imaging; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008382:Marfan Syndrome / Q000000981:diagnostic imaging / Q000235:genetics*; D008875:Middle Aged; D009333:Neck / Q000000981:diagnostic imaging; D010641:Phenotype; D011379:Prognosis; D000073359:Exome Sequencing