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Hereditary haemorrhagic telangiectasia and SMAD4 mutation in a patient with complex single ventricle heart disease

Published online by Cambridge University Press:  09 October 2023

Madison A. Grasty Open the ORCID record for Madison A. Grasty [Opens in a new window] ,
Constantine D. Mavroudis ,
Aaron G. DeWitt ,
Benjamin W. Kozyak ,
Peter Mamula ,
Suzanne P. MacFarland ,
Muhammad A.K. Nuri ,
Lindsay S. Rogers ,
Jonathan J. Rome  and
J. William Gaynor
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Madison A. Grasty
Affiliation:
Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
Constantine D. Mavroudis
Affiliation:
Divisions of Cardiothoracic Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Aaron G. DeWitt
Affiliation:
Cardiac Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Benjamin W. Kozyak
Affiliation:
Cardiac Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Peter Mamula
Affiliation:
Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Suzanne P. MacFarland
Affiliation:
Division of Oncology and Cancer Predisposition Program, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Muhammad A.K. Nuri
Affiliation:
Divisions of Cardiothoracic Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Lindsay S. Rogers
Affiliation:
Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Jonathan J. Rome
Affiliation:
Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
J. William Gaynor
Affiliation:
Divisions of Cardiothoracic Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
David J. Goldberg*
Affiliation:
Cardiac Center and Fetal Heart Program, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
*
Corresponding author: D. J. Goldberg; Email: goldbergda@chop.edu
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Abstract

We report a case of hypoplastic left heart syndrome and with subsequent aortopathy and then found to have hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome due to a germline SMAD4 pathologic variant. The patient’s staged palliation was complicated by the development of neoaortic aneurysms, arteriovenous malformations, and gastrointestinal bleeding thought to be secondary to Fontan circulation, but workup revealed a SMAD4 variant consistent with hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome. This case underscores the importance of genetic modifiers in CHD, especially those with Fontan physiology.

Keywords

Hereditary haemorrhagic telangiectasiaSMAD 4Fontanaortopathy

Information

Type
Brief Report
Information
Cardiology in the Young , Volume 33 , Issue 12 , December 2023 , pp. 2667 - 2669
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Copyright
© The Author(s), 2023. Published by Cambridge University Press

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References

Shovlin, CL, Guttmacher, AE, Buscarini, E, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-osler-weber syndrome). Am J Med Genet 2000; 91: 66–67.3.0.CO;2-P>CrossRefGoogle ScholarPubMed
Heald, B, Rigelsky, C, Moran, R, et al. Prevalence of thoracic aortopathy in patients with juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia due to SMAD4. Am J Med Genet A 2015; 167A: 1758–1762.CrossRefGoogle ScholarPubMed
Teekakirikul, P, Milewicz, DM, Miller, DT, et al. Thoracic aortic disease in two patients with juvenile polyposis syndrome and SMAD4 mutations. Am J Med Genet A 2013; 161A: 185–191.CrossRefGoogle ScholarPubMed
Gallione, CJ, Repetto, GM, Legius, E, et al. A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet 2004; 363: 852–859.CrossRefGoogle Scholar
Blatter, R, Tschupp, B, Aretz, S, et al. Disease expression in juvenile polyposis syndrome: a retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers. Genet Med 2020; 22: 1524–1532.CrossRefGoogle ScholarPubMed
Kojima, T, Kuwata, S, Kurishima, C, et al. Aortic root dilation and aortic stiffness in patients with single ventricular circulation. Circ J 2014; 78: 2507–2511.CrossRefGoogle ScholarPubMed
Kim, YY, Rathod, RH, Gauvreau, K, et al. Factors associated with severe aortic dilation in patients with Fontan palliation. Heart 2017; 103: 280–286.CrossRefGoogle ScholarPubMed
Cohen, MS, Marino, BS, McElhinney, DB, et al. Neo-aortic root dilation and valve regurgitation up to 21 years after staged reconstruction for hypoplastic left heart syndrome. J Am Coll Cardiol 2003; 42: 533–540.CrossRefGoogle ScholarPubMed