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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.

Background & Aims: Desmoid tumors are non-metastasizing fibromatoses that occur in 10%-20% of subjects with familial adenomatous polyposis (FAP). Intra-abdominal desmoid tumors are a major cause of mortality in FAP. FAP-associated desmoid tumors are linked to trauma, particularly abdominal surgery, family history of desmoids, hormonal factors, and the location of the APC mutation. We hypothesized that prophylactic colectomy at an early age might increase the risk of developing desmoids. The aim of this study was to determine whether colectomy earlier in life is a risk factor for the development of desmoid tumors., Methods: An analysis was made of the association between development of desmoid and age at colectomy, family history of desmoids, gender, and APC mutation in FAP patients in the Registry (1980-2005) at Mount Sinai Hospital, Toronto, Ontario, Canada., Results: FAP patients (n = 930) from 365 kindreds were identified. Desmoid prevalence was 14% (n = 121). Female patients were more likely to develop desmoids than male patients (17% vs 11%, P = .03). Female patients who had an early colectomy were more than 2 times more likely to develop a desmoid, compared with women who had a colectomy at >18 years (P = .01). Early colectomy did not increase risk of developing a desmoid in male patients (P = .42). Female patients who had an early colectomy (