Document Type
Article
Publication Date
7-2024
Identifier
DOI: 10.1002/jpn3.12257
Abstract
OBJECTIVE: A 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.
METHODS: Demographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group.
RESULTS: A 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.
CONCLUSIONS: This 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.
Journal Title
Journal of pediatric gastroenterology and nutrition
Volume
79
Issue
1
First Page
161
Last Page
167
MeSH Keywords
Humans; Smad4 Protein; Bone Morphogenetic Protein Receptors, Type I; Child; Male; Female; Intestinal Polyposis; Adolescent; Phenotype; Mutation; Neoplastic Syndromes, Hereditary; Child, Preschool; Follow-Up Studies
Keywords
JPS; hamartomatous‐polyp; pediatric
Recommended Citation
Cohen S, Yerushalmy-Feler A, Rojas I, et al. Juvenile polyposis syndrome in children: The impact of SMAD4 and BMPR1A mutations on clinical phenotype and polyp burden. J Pediatr Gastroenterol Nutr. 2024;79(1):161-167. doi:10.1002/jpn3.12257
Comments
Grants and funding
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Publisher's Link: https://onlinelibrary.wiley.com/doi/10.1002/jpn3.12257