SMAD4 mutation and the combined juvenile polyposis and hereditary hemorrhage telangiectasia syndrome: a single center experience

Abstract

Purpose

Mutations of the SMAD4 gene can result in a distinct syndrome with combined clinical features of both juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT). Even though it is known that patients with the overlap syndrome are at increased risk for colorectal malignancies and bleeding, the outcomes of this patient population have not been extensively studied.

Methods

Retrospective study aiming to describe the phenotype and clinical outcomes of patients with genetically confirmed JP–HHT combined syndrome in a single large tertiary center in North America.

Results

A total of 22 patients were identified, the majority females (59%) with a median age diagnosis at 24 years. Polyps were more commonly seen in the lower gastrointestinal (GI) tract, and tubular adenomas were seen in 50%. Epistaxis and pulmonary arteriovenous malformations (AVM) were the most common manifestations of HHT, with a median Curacao score of 3 [1–4]. Hospitalization for gastrointestinal bleeding and cerebrovascular events occurred at a rate of 28% and 4%, respectively. Two patients had GI malignancies, one rectal and one small bowel adenocarcinoma. Overall mortality was 14%.

Conclusions

Patients with the combined JP–HHT syndrome remain at risk for life-threatening vascular complications and gastrointestinal malignancies; close follow-up is necessary to minimize morbidity and mortality in this patient population.