Novel SMAD3 Mutation in a Patient with Hypoplastic Left Heart Syndrome with Significant Aortic Aneurysm

Aneurysms-osteoarthritis syndrome (AOS) caused by haploinsufficiency of SMAD3 is a recently described cause of syndromic familial thoracic aortic aneurysm and dissection (TAAD). We identified a novel SMAD3 mutation in a patient with hypoplastic left heart syndrome (HLHS) who developed progressive aortic aneurysm requiring surgical replacement of the neoaortic root, ascending aorta, and proximal aortic arch. Family screening for the mutation revealed that his father, who has vascular and skeletal features of AOS, and his brother, who is asymptomatic, also have the pathogenic mutation. This is the first case report of a SMAD3 mutation in a patient with hypoplastic left heart syndrome. This case highlights the importance of genetic testing for known causes of aneurysm in patients with congenital heart disease who develop aneurysmal disease as it may significantly impact the management of those patients and their family members.

• Publication year

  2014

• Venue

  Case Reports in Genetics

• Publication date

  2014-03-03

• Fields of study

  Medicine

• Identifiers
  DOI 10.1155/2014/591516PMID 24711937PMCID 3970455
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Thoracic Aortic Aneurysm in Infancy in Aneurysms–Osteoarthritis Syndrome Due to a Novel SMAD3 Mutation: Further Delineation of the Phenotype

  2013cited by this paper
• An unanticipated copy number variant of chromosome 15 disrupting SMAD3 reveals a three‐generation family at serious risk for aortic dissection

  2013cited by this paper
• Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm

  2012cited by this paper
• TGFB2 loss of function mutations cause familial thoracic aortic aneurysms and acute aortic dissections associated with mild systemic features of the Marfan syndrome

  2012cited by this paper
• Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis

  2011cited by this paper
• Root dilation in patients with truncus arteriosus.

  2011cited by this paper
• Phenotypic spectrum of the SMAD3-related aneurysms–osteoarthritis syndrome

  2011cited by this paper
• Mutations in myosin light chain kinase cause familial aortic dissections.

  2010cited by this paper
• Aortic Dissection in the Adult Fontan with Aortic Root Enlargement

  2009cited by this paper
• Ross operation: 16-year experience.

  2008cited by this paper
• Mutations in smooth muscle α-actin (ACTA2) lead to thoracic aortic aneurysms and dissections

  2007cited by this paper
• Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus

  2006cited by this paper
• Aortic root dilation and aortic elastic properties in children after repair of tetralogy of Fallot.

  2006cited by this paper
• Neo-aortic valvar function after the arterial switch

  2006cited by this paper
• Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome

  2006cited by this paper
• A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2

  2005cited by this paper
• Neo-aortic root dilation and valve regurgitation up to 21 years after staged reconstruction for hypoplastic left heart syndrome.

  2003cited by this paper
• Reduced penetrance and variable expressivity of familial thoracic aortic aneurysms/dissections.

  1998cited by this paper
• Growth of the Aortic Anastomosis, Annulus, and Root After the Arterial Switch Procedure Performed in Infancy

  1993cited by this paper
• Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene

  1991cited by this paper

• Neoaortic Dilation and Polyvalvar Dysfunction: The Coexistence of Marfan Syndrome with Hypoplastic Left Heart Syndrome

  2025cites this paper
• Sexual dimorphism in SMAD3 pathogenic variant-harbouring individuals

  2025cites this paper
• Total Aortic Arch and Neoaortic Root Replacement Following Stage III Palliation for Hypoplastic Left Heart Syndrome

  2024cites this paper
• Comprehensive management of type A acute aortic dissection in the paediatric population with ACTA 2 mutation: case reports and literature review of paediatric aortic dissection.

  2023cites this paper
• Cardiac Development: A Glimpse on Its Translational Contributions

  2021cites this paper
• The first reported case of Loeys‐Dietz syndrome in a patient with biallelic SMAD3 variants

  2020cites this paper
• Clinical and genetic data of 22 new patients with SMAD3 pathogenic variants and review of the literature

  2020cites this paper
• Grandparental genotyping enhances exome variant interpretation

  2020cites this paper
• SMAD3 pathogenic variants: risk for thoracic aortic disease and associated complications from the Montalcino Aortic Consortium

  2019cites this paper
• A mutation update on the LDS‐associated genes TGFB2/3 and SMAD2/3

  2018cites this paper
• Aortic root and hemiarch replacement in a patient with Loeys-Dietz and hypoplastic left heart syndromes.

  2018cites this paper
• Chapter 3 – Systemic Features of Aneurysms-Osteoarthritis Syndrome

  2017cites this paper
• A novel SMAD3 mutation caused multiple aneurysms in a patient without osteoarthritis symptoms.

  2017cites this paper
• Chapter 2 – Cardiovascular Phenotype of Aneurysms-Osteoarthritis Syndrome

  2017cites this paper
• Human Genetics of Hypoplastic Left Heart Syndrome

  2016cites this paper
• Fishing for genes : a disease transgressing approach to unravel the genetic basis of thoracic aortic aneurysm

  2016influential citation
• Defective Connective Tissue Remodeling in Smad3 Mice Leads to Accelerated Aneurysmal Growth Through Disturbed Downstream TGF-β Signaling

  2016cites this paper
• A Novel Mutation of SMAD3 Identified in a Chinese Family with Aneurysms-Osteoarthritis Syndrome

  2015cites this paper
• Endocardial fibroelastosis is caused by aberrant endothelial to mesenchymal transition.

  2015cites this paper
• SMAD2 Mutations Are Associated with Arterial Aneurysms and Dissections

  2015cites this paper
• Familial thoracic aortic aneurysms

  2014cites this paper
• Smad3 plays an inhibitory role in phosphate-induced vascular smooth muscle cell calcification.

  2014cites this paper