Juvenile polyposis, hereditary hemorrhagic telangiectasia, and early onset colorectal cancer in patients with SMAD4 mutation |
| |
Authors: | Frank Schwenter Marie E Faughnan Abigail B Gradinger Terri Berk Robert Gryfe Aaron Pollett Zane Cohen Steven Gallinger Carol Durno |
| |
Institution: | Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON M5T 3L9, Canada. frank.schwenter@gmail.com |
| |
Abstract: | Background Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder most often caused by mutation in the endoglin or ALK1 genes. A distinct syndrome combines the clinical features of HHT and juvenile polyposis (JP) and has been associated with SMAD4 mutation. The aim of this study was to describe the phenotype of patients with JP–HHT and SMAD4 mutations and to compare this phenotype with HHT or JP patients with mutations other than SMAD4. Methods Patients prospectively enrolled in the Toronto HHT and JP databases who underwent genotyping were included. The phenotypic characteristics of JP–HHT patients with SMAD4 mutations and patients with mutations other than SMAD4 were analyzed and compared. Results Three hundred and fifty-eight patients underwent genetic testing (HHT, n?=?332; JP, n?=?26). Among fourteen patients identified with SMAD4 mutations, ten met the clinical diagnostic criteria for both JP and HHT (71%). Patients with SMAD4 mutations had 100% penetrance of the polyposis phenotype. All patients with JP and SMAD4 mutation had features of HHT. Three JP–HHT patients developed early onset colorectal cancer (CRC) (mean age 28 years). JP–HHT patients with SMAD4 mutation had a significantly higher rate of anemia than HHT patients with mutations other than SMAD4. Conclusions Patients with HHT and SMAD4 mutations are at significant risk of JP and CRC. The gastrointestinal phenotype is similar to JP patients without SMAD4 mutation. It is essential for HHT patients to undergo genetic testing to determine if they have SMAD4 mutations so that appropriate gastrointestinal screening and surveillance for JP and CRC can be completed. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|