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Genet Med. 2018 Oct;20(10):1206-1215. doi: 10.1038/gim.2017.245. Epub 2018 Jan 4.

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

Author information

1
Department of Internal Medicine, University of Texas Health Science Center at Houston McGovern Medical School, Houston, USA, Texas.
2
Center for Medical Genetics, University Hospital Ghent, Ghent, Belgium.
3
Cardiovascular Division, Washington University School of Medicine, St. Louis, USA, Missouri.
4
Division of Pediatrics and Child Health, University of Sydney, Sydney, Australia, New South Wales.
5
Department of Pediatrics, The University of Utah School of Medicine, Salt Lake City, USA, Utah.
6
Division of Cardiology, Department of Pediatrics, University of Saskatchewan, Saskatoon, Canada, Saskatchewan.
7
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA, Texas.
8
Department of Pediatrics, University of Colorado School of Medicine, Aurora, USA, Colorado.
9
Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK.
10
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, USA, Oregon.
11
Department of Pediatrics, Oregon Health and Science University, Portland, USA, Oregon.
12
Department of Pediatrics, Emory University School of Medicine, Atlanta, USA, Georgia.
13
Department of Ophthalmology, Justus-Liebig-University Giessen, Giessen, Germany.
14
Department of Medical Genetics, Spectrum Health, Grand Rapids, USA, Michigan.
15
Tokyo University of Technology School of Health Sciences, Tokyo, Japan.
16
Department of Medical Genetics, Sakakibara Heart Institute, Tokyo, Japan.
17
Texas Children's Hospital, Baylor College of Medicine, Houston, USA, Texas.
18
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, USA, Ohio.
19
Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
20
Department of Medical Genetics, Children's Hospital of Eastern Ontario, Ottawa, Canada, Ontario.
21
Department of Surgery, University of Washington, Seattle, USA, Washington.
22
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, USA, Florida.
23
Department of Cardiothoracic and Vascular Surgery, University of Texas Health Science Center at Houston McGovern Medical School, Houston, USA, Texas.
24
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, USA, Massachusetts.
25
Department of Pediatrics, Children's Hospital & Medical Center, University of Nebraska, Omaha, USA, Nebraska.
26
Perelman School of Medicine at the, University of Pennsylvania, Philadelphia, USA, Pennsylvania.
27
Department of Internal Medicine, University of Texas Health Science Center at Houston McGovern Medical School, Houston, USA, Texas. Dianna.M.Milewicz@uth.tmc.edu.

Abstract

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.

KEYWORDS:

ACTA2; congenital mydriasis; patent ductus arteriosus; smooth muscle dysfunction syndrome; thoracic aortic aneurysm

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