{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:27:14Z","timestamp":1791296834740,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T00:00:00Z","timestamp":1430352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:sec><jats:label\/><jats:p>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 (<jats:italic>ACVRL1, ENG<\/jats:italic>, and <jats:italic>SMAD4<\/jats:italic>) are members of the TGF\u03b2 pathway. Other syndromes associated with abnormalities in TGF\u03b2 signaling include Marfan syndrome, Loeys\u2013Dietz 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 <jats:italic>ACVRL1, ENG<\/jats:italic>, or <jats:italic>SMAD4<\/jats:italic> and underwent echocardiogram. Two\u2010dimensional 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\u2010six patients from 15 families (one <jats:italic>ACVRL1<\/jats:italic>, four <jats:italic>ENG<\/jats:italic>, eight <jats:italic>SMAD4<\/jats:italic>, and two clinical diagnoses) were included in the analysis. Aortopathy was found in 6\/26 (23%) patients; all had <jats:italic>SMAD4<\/jats:italic> mutations. In our cohort, 6\/16 (38%) <jats:italic>SMAD4<\/jats:italic> mutation carriers had evidence of aortopathy. These data suggest that aortopathy could be part of the spectrum of <jats:italic>SMAD4<\/jats:italic>\u2010induced HHT manifestations. Routine aortic imaging, including measurements of the aorta, should be considered in patients with <jats:italic>SMAD4<\/jats:italic> mutations to allow for appropriate medical and surgical recommendations. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37093","type":"journal-article","created":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T14:16:02Z","timestamp":1430403362000},"page":"1758-1762","source":"Crossref","is-referenced-by-count":72,"title":["Prevalence of thoracic aortopathy in patients with juvenile Polyposis Syndrome\u2010Hereditary Hemorrhagic Telangiectasia due to <i>SMAD4<\/i>"],"prefix":"10.1002","volume":"167","author":[{"given":"Brandie","family":"Heald","sequence":"first","affiliation":[{"name":"Genomic Medicine Institute Cleveland Clinic  Cleveland Ohio"},{"name":"Sanford R Weiss Center for Hereditary Colorectal Cancer Neoplasia Cleveland Clinic  Cleveland 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Cleveland Clinic  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Burke","sequence":"additional","affiliation":[{"name":"Sanford R Weiss Center for Hereditary Colorectal Cancer Neoplasia Cleveland Clinic  Cleveland Ohio"},{"name":"Digestive Disease Institute Cleveland Clinic  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Zahka","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Cleveland Clinic  Cleveland Ohio"},{"name":"Heart and Vascular Institute Cleveland Clinic  Cleveland 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