The prevalence of hereditary hemorrhagic telangiectasia in Juvenile Polyposis syndrome patients with SMAD4 mutations

Background Juvenile Polyposis Syndrome (JPS) is defined by the presence of ≥ 5 colorectal juvenile polyps or any number of juvenile polyps in an individual with a family history of JPS. Genetic alterations including either point mutations or large rearrangements in BMPR1A or SMAD4 are found in 50% of affected individuals. Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease diagnosed upon the presence of epistaxis, visceral arteriovenous malformations (AVM) or mucutaneous telangiectasias. HHT is diagnosed when there are ≥ 3 manifestations and is suspected when there are at least 2 manifestations. Most HHT cases are caused by a germline mutation in ALK1 or ENG, members of the TGFb signaling pathway. Approximately 22% of patients with Juvenile Polyposis Syndrome (JPS) due to a SMAD4 mutation have been reported to also have HHT [1]. Most prior publications have few patients and no systematic approach to screening, so the true incidence of the combined JPS/HHT syndrome is not known. Our aim was to determine the prevalence of HHT in our patients with JPS with a SMAD4 mutation including those who underwent systematic screening for AVM’s.