S Cohen et al. J Pediatr Gastroenterol Nutr.2024;79:161‐167. Open Access! Juvenile polyposis syndrome in children: The impact of SMAD4 and BMPR1A mutations on clinical phenotype and polyp burden

One of the authors on this paper is Dr. Erdman (see yesterday’s post: Dr. Steve Erdman: Perplexing Polyposis Patients: a Case-Based Discussion).

Background/Methods: A constitutional disease‐causing variant (DCV) in the SMAD4 or BMPR1A genes is present in 40%–60% of patients with juvenile polyposis syndrome (JPS). 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

Key findings:

• DCV‐positive children were diagnosed at an older age compared to DCV‐negative children [median 12 years vs. 5 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). All operations in the DCV‐positive group were performed in patients with SMAD4 mutations
• DCV-positive children had more frequent new polyps: average of 12.2 versus 2 new polyps for every year of follow‐up
• DCV-positive children had a lower frequency of rectal bleeding (56% compared to 93%) which could be a factor in later presentation
• There was no difference in the burden of polyps between patients with SMAD4 and BMPR1A mutations. A higher frequency of gastric polyps was observed in the SMAD4 group (55.3%vs. 9.1% for the patients in the BMPR1A group ,p = 0.004). . HHT was observed only in the SMAD4 mutations group (20.7% vs. 0 in the BMPR1Agroup. p = 0.024)

My take: Children with DCV-positive JPS likely require more frequent surveillance than DCV-negative JPS.

Related blog posts:

• Review: Polyposis in Pediatrics
• Surprising Genetic Mutations in Polyposis Study
• What I Like About ESPGHAN Familial Adenomatous Polyposis Guidelines These recommendations, however, suggest starting screening at 12-14 years.
• ESPGHAN Juvenile Polyposis Syndrome Recommendations  These recommendations are different in that they do not recommend EGD in the pediatric age group: “Surveillance of the upper GI tract in affected or at-risk JPS patients is not required in childhood or teenage years, unless there is unexplained anaemia or upper GI symptoms.”
• ESPGHAN Peutz-Jeghers syndrome Guidelines
• Are You Familiar with CMMR-D? The term CMMR-D refers to constitutional mismatch repair deficiency.  This occurs when an individual inherits two MMR gene defects (rather than one gene defect in Lynch syndrome); with CMMR-D screening recommendations include yearly endoscopic evaluation beginning at age 3 years or at diagnosis.
• Updated Guidelines on Genetic Testing/management for Hereditary GI Cancer Syndromes