John Rosendahl Østergaard

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Ellen S Regalado, Department of Internal Medicine, University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA.
  • ,
  • Lauren Mellor-Crummey, Department of Internal Medicine, University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA.
  • ,
  • Julie De Backer, Center for Medical Genetics, University Hospital Ghent, Ghent, Belgium.
  • ,
  • Alan C Braverman, Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.
  • ,
  • Lesley Ades, Division of Pediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia.
  • ,
  • Susan Benedict, Department of Pediatrics, The University of Utah School of Medicine, Salt Lake City, Utah, USA.
  • ,
  • Timothy J Bradley, Division of Cardiology, Department of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
  • ,
  • M Elizabeth Brickner, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  • ,
  • Kathryn C Chatfield, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
  • ,
  • Anne Child, Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK.
  • ,
  • Cori Feist, Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon, USA.
  • ,
  • Kathryn W Holmes, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
  • ,
  • Glen Iannucci, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
  • ,
  • Birgit Lorenz, Department of Ophthalmology, Justus-Liebig-University Giessen, Giessen, Germany.
  • ,
  • Paul Mark, Department of Medical Genetics, Spectrum Health, Grand Rapids, Michigan, USA.
  • ,
  • Takayuki Morisaki, Tokyo University of Technology School of Health Sciences, Tokyo, Japan.
  • ,
  • Hiroko Morisaki, Department of Medical Genetics, Sakakibara Heart Institute, Tokyo, Japan.
  • ,
  • Shaine A Morris, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
  • ,
  • Anna L Mitchell, Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
  • ,
  • John R Ostergaard
  • Julie Richer, Department of Medical Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
  • ,
  • Denver Sallee, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
  • ,
  • Sherene Shalhub, Department of Neurological Surgery, University of Washington, Seattle, Washington, USA.
  • ,
  • Mustafa Tekin, John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.
  • ,
  • Anthony Estrera, Department of Cardiothoracic and Vascular Surgery, University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA.
  • ,
  • Patricia Musolino, Department of Neurosurgery, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, 1007 MB Amsterdam, the Netherlands; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • ,
  • Anji Yetman, Department of Pediatrics, Children's Hospital & Medical Center, University of Nebraska, Omaha, Nebraska, USA.
  • ,
  • Reed Pyeritz, Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
  • ,
  • Dianna M Milewicz, Department of Internal Medicine, University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA.
  • ,
  • Montalcino Aortic Consortium

Purpose: Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle–dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management. Methods: Medical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed. Results: All patients had congenital mydriasis and related pupillary abnormalities at birth and presented in infancy with a patent ductus arteriosus or aortopulmonary window. Patients had cerebrovascular disease characterized by small vessel disease (hyperintense periventricular white matter lesions; 95%), intracranial artery stenosis (77%), ischemic strokes (27%), and seizures (18%). Twelve (36%) patients had thoracic aortic aneurysm repair or dissection at median age of 14 years and aortic disease was fully penetrant by the age of 25 years. Three (9%) patients had axillary artery aneurysms complicated by thromboembolic episodes. Nine patients died between the ages of 0.5 and 32 years due to aortic, pulmonary, or stroke complications, or unknown causes. Conclusion: Based on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early-onset life-threatening complications.

Original languageEnglish
JournalGenetics in Medicine
Volume20
Issue10
Pages (from-to)1206-1215
Number of pages10
ISSN1098-3600
DOIs
Publication statusPublished - Oct 2018

    Research areas

  • Actins/genetics, Adolescent, Adult, Aortic Aneurysm, Thoracic/diagnosis, Arginine/genetics, Child, Child, Preschool, Ductus Arteriosus, Patent/diagnosis, Eye Diseases, Hereditary/diagnosis, Genetic Predisposition to Disease, Genetic Testing, Humans, Infant, Medical Records, Muscle, Smooth/diagnostic imaging, Mydriasis/diagnosis, Young Adult

See relations at Aarhus University Citationformats

ID: 121352765