• Margaret O'Malley, Lisa LaGuardia, Matthew F Kalady, Joseph Parambil, Brandie Heald, Charis Eng, James Church, and Carol A Burke.
• Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia in the Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
• Dis. Colon Rectum. 2012 Aug 1; 55 (8): 886-92.

BackgroundJuvenile polyposis syndrome is a dominant GI polyposis syndrome defined by ≥ 5 GI juvenile polyps or ≥ 1 juvenile polyps with a family history of juvenile polyposis. Mutations in BMPR1A or SMAD4 are found in 50% of individuals. Hereditary hemorrhagic telangiectasia is a dominant disorder characterized by epistaxis, visceral arteriovenous malformations, and telangiectasias. Hereditary hemorrhagic telangiectasia is diagnosed when ≥ 3 criteria including clinical manifestations or a family history, are present. A juvenile polyposis-hereditary hemorrhagic telangiectasia overlap syndrome has previously been reported in 22% of patients with juvenile polyposis due to a SMAD4 mutation.ObjectiveOur objective was to determine the prevalence and clinical manifestations of hereditary hemorrhagic telangiectasia by Curacao criteria in our juvenile polyposis SMAD4 patients.Design, Patients, And SettingThis was a cohort study of juvenile polyposis patients in our inherited colon cancer registries. Hereditary hemorrhagic telangiectasia manifestations were obtained from medical records, patient contact, and/or prospective hereditary hemorrhagic telangiectasia screening. The Curacao criteria was used for diagnosis of hereditary hemorrhagic telangiectasia (≥ 3 criteria diagnostic; 2 criteria suspect of).Main Outcome MeasuresPrevalence and clinical manifestations of hereditary hemorrhagic telangiectasia in juvenile polyposis SMAD4 patients.ResultsForty-one juvenile polyposis families were identified. Genetic testing was available for individuals within 18 families. SMAD4 mutations were found in 21 relatives in 9 families. Eighty-one percent of SMAD4 patients had hereditary hemorrhagic telangiectasia and 14% were suspected of having hereditary hemorrhagic telangiectasia. Epistaxis and asthma are the most common symptoms in our overlap patients. Symptomatic and subclinical arteriovenous malformations were noted near universally.LimitationsThere was a single, tertiary referral center.ConclusionsNearly all juvenile polyposis SMAD4 patients have the overlap syndrome. The clinical implications and need for hereditary hemorrhagic telangiectasia screening are important factors for genetic testing in juvenile polyposis. Health care providers must be cognizant of the juvenile polyposis-hereditary hemorrhagic telangiectasia overlap syndrome and the implications for management of these patients.

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