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

• Published in: American journal of medical genetics. Part A Vol. 167A; no. 8; pp. 1758 - 1762
• Main Authors: Heald, Brandie, Rigelsky, Christina, Moran, Rocio, LaGuardia, Lisa, O'Malley, Margaret, Burke, Carol A., Zahka, Kenneth
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-08-2015; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Aorta, Thoracic - pathology; aortic aneurysm; Aortic Diseases - complications; Aortic Diseases - pathology; Female; hereditary hemorrhagic telangiectasia; Humans; Intestinal Polyposis - complications; juvenile polyposis syndrome; Male; Prevalence; Smad4 Protein - physiology; Telangiectasia, Hereditary Hemorrhagic - complications; TGFβ pathway; Young Adult; TGFβ pathway; aortic aneurysm; hereditary hemorrhagic telangiectasia; juvenile polyposis syndrome
• ISSN: 1552-4825; 1552-4833
• 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 TGFβ pathway. Other syndromes associated with abnormalities in TGFβ 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. © 2015 Wiley Periodicals, Inc.