Juvenile polyposis syndrome in children: The impact of SMAD4 and BMPR1A mutations on clinical phenotype and polyp burden

Abstract

AbstractObjectiveA constitutional disease‐causing variant (DCV) in the SMAD4 or BMPR1A genes is present in 40%–60% of patients with juvenile polyposis syndrome (JPS). The aim of this study was to characterize the clinical course and polyp burden in children with DCV‐positive JPS compared to DCV‐negative JPS.MethodsDemographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group.ResultsA total of 124 children with JPS were included: 69 (56%) DCV‐negative and 55 (44%) DCV‐positive (53% SMAD4 and 47% BMPR1A) with a median (interquartile range) follow‐up of 4 (2.8–6.4) years. DCV‐positive children were diagnosed at an older age compared to DCV‐negative children [12 (8–15.7) years vs. 5 (4–7) years, respectively, p < 0.001], had a higher frequency of family history of polyposis syndromes (50.9% vs. 1.4%, p < 0.001), experienced a greater frequency of extraintestinal manifestations (27.3% vs. 5.8%, p < 0.001), and underwent more gastrointestinal surgeries (16.4% vs. 1.4%, p = 0.002). The incidence rate ratio for the development of new colonic polyps was 6.15 (95% confidence interval 3.93–9.63, p < 0.001) in the DCV‐positive group compared to the DCV‐negative group, with an average of 12.2 versus 2 new polyps for every year of follow‐up. There was no difference in the burden of polyps between patients with SMAD4 and BMPR1A mutations.ConclusionsThis largest international cohort of pediatric JPS revealed that DCV‐positive and DCV‐negative children exhibit distinct clinical phenotype. These findings suggest a potential need of differentiated surveillance strategies based upon mutation status.