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Prevalence of thoracic aortopathy in patients with juvenile Polyposis Syndrome-Hereditary Hemorrhagic Telangiectasia due to SMAD4.

Authors: Heald, B  Rigelsky, C  Moran, R  LaGuardia, L  O'Malley, M  Burke, CA  Zahka, K 
Citation: Heald B, etal., Am J Med Genet A. 2015 Aug;167A(8):1758-62. doi: 10.1002/ajmg.a.37093. Epub 2015 Apr 30.
Pubmed: (View Article at PubMed) PMID:25931195
DOI: Full-text: DOI:10.1002/ajmg.a.37093

Hereditary hemorrhagic telangiectasia (HHT) is characterized by abnormal vascular structures that may present as epistaxis, telangiectasias, and/or arteriovenous malformations. The genes associated with HHT (ACVRL1, ENG, and SMAD4) are members of the TGFbeta pathway. Other syndromes associated with abnormalities in TGFbeta signaling include Marfan syndrome, Loeys-Dietz syndrome and related disorders. These disorders have aortic disease as a prominent finding. While there are case reports of patients with HHT and aortopathy (dilatation/aneurysm, dissection, and rupture), this has not been systematically investigated. We conducted a retrospective chart review to determine the prevalence of aortopathy in an HHT cohort. Patients from a single institution were identified who met the Curacao Criteria for a clinical diagnosis of HHT and/or had a mutation in ACVRL1, ENG, or SMAD4 and underwent echocardiogram. Two-dimensional echocardiograms were reviewed by a single pediatric cardiologist, and data were collected on demographics, genotype, HHT features, aortic root measurements, past medical history, and family history. Z scores and nomograms were utilized to identify abnormal results. Twenty-six patients from 15 families (one ACVRL1, four ENG, eight SMAD4, and two clinical diagnoses) were included in the analysis. Aortopathy was found in 6/26 (23%) patients; all had SMAD4 mutations. In our cohort, 6/16 (38%) SMAD4 mutation carriers had evidence of aortopathy. These data suggest that aortopathy could be part of the spectrum of SMAD4-induced HHT manifestations. Routine aortic imaging, including measurements of the aorta, should be considered in patients with SMAD4 mutations to allow for appropriate medical and surgical recommendations.


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CRRD Object Information
CRRD ID: 11062588
Created: 2016-04-27
Species: All species
Last Modified: 2016-04-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.