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

Montalcino Aortic Consortium

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1206-1215
Number of pages10
JournalGenetics in Medicine
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Smooth Muscle
Arginine
Patent Ductus Arteriosus
Aneurysm
Stroke
Axillary Artery
Thoracic Aortic Aneurysm
Cerebrovascular Disorders
Aortic Diseases
Pulmonary Hypertension
Medical Records
Dissection
Pathologic Constriction
Seizures
Arteries
History
Parturition
Lung

Keywords

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

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

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

In: Genetics in Medicine, Vol. 20, No. 10, 01.10.2018, p. 1206-1215.

Research output: Contribution to journalArticle

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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",
author = "{Montalcino Aortic Consortium} and Regalado, {Ellen S.} and Lauren Mellor-Crummey and {De Backer}, Julie and Braverman, {Alan C.} and Lesley Ades and Susan Benedict and Bradley, {Timothy J.} and Brickner, {M. Elizabeth} and Chatfield, {Kathryn C.} and Anne Child and Cori Feist and Kathryn Holmes and Glen Iannucci and Birgit Lorenz and Paul Mark and Takayuki Morisaki and Hiroko Morisaki and Morris, {Shaine A.} and Mitchell, {Anna L.} and Ostergaard, {John R.} and Julie Richer and Denver Sallee and Sherene Shalhub and Mustafa Tekin and Anthony Estrera and Patricia Musolino and Anji Yetman and Reed Pyeritz and Milewicz, {Dianna M.}",
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AU - Regalado, Ellen S.

AU - Mellor-Crummey, Lauren

AU - De Backer, Julie

AU - Braverman, Alan C.

AU - Ades, Lesley

AU - Benedict, Susan

AU - Bradley, Timothy J.

AU - Brickner, M. Elizabeth

AU - Chatfield, Kathryn C.

AU - Child, Anne

AU - Feist, Cori

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AU - Iannucci, Glen

AU - Lorenz, Birgit

AU - Mark, Paul

AU - Morisaki, Takayuki

AU - Morisaki, Hiroko

AU - Morris, Shaine A.

AU - Mitchell, Anna L.

AU - Ostergaard, John R.

AU - Richer, Julie

AU - Sallee, Denver

AU - Shalhub, Sherene

AU - Tekin, Mustafa

AU - Estrera, Anthony

AU - Musolino, Patricia

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N2 - 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.

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