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Author Notes:

Corresponding author: Dianna M. Milewicz, MD, PhD, 6431 Fannin Street MSB 6.100, Houston, TX 77030, USA, Tel.: +713 500 6715; fax: +713 500 0693, Dianna.M.Milewicz@uth.tmc.edu.

Acknowledgments: We are grateful to the patients and families who participated in this study.

Disclosure: The authors declare no conflict of interest.


Research Funding:

This research is supported by the National Institutes of Health (R01 HL62594), the John Ritter Foundation, Genetic Aortic Disorders Association (GADA), and the Temerty Family Foundation.


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

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

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Journal Title:

Genetics in Medicine


Type of Work:

Article | Post-print: After Peer Review


PurposeSmooth 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.MethodsMedical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed.ResultsAll 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.ConclusionBased on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early-onset life-threatening complications.

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