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Objectives: Loss-of-function mutations of BMPR1A cause juvenile polyposis syndrome (JPS), but large genomic deletions in BMPR1A are rare, reported in few families only, and data regarding the associated phenotype are limited., Methods: We investigated clinical features and genomic data of 7 extended seemingly unrelated families with a genomic deletion of the entire coding region of BMPR1A. We defined mutation size, mutation prevalence, and tumor pathogenesis using whole-genome sequencing, targeted genotyping, and haplotype analysis., Results: Patients with JPS from 7 families of Bukharin Jewish ancestry carried a deletion of 429 kb, encompassing the BMPR1A coding sequence and 8 downstream genes. Haplotype analysis and testing controls identified this as a common founder mutation occurring in 1/124 individuals of Bukharin origin. Tumor testing did not demonstrate loss of heterozygosity. Among carriers, JPS was almost fully penetrant, but clinical features varied widely, ranging from mild to very severe, including pan-enteric polyps, gastritis, and colorectal, esophageal, and testicular cancer, and carriers with phenotypes, which would not have raised suspicion of JPS., Discussion: The phenotype in this large cohort was extremely variable, although all carriers shared the same variant and the same genetic background. New observations include a preponderance of adenomatous rather than juvenile polyps, possible association with testicular cancer, and unexpected upper gastrointestinal involvement.

Background & Aims: Despite the availability of endoscopic therapy, many patients in the United States undergo surgical resection for nonmalignant colorectal polyps. We aimed to quantify and examine trends in the use of surgery for nonmalignant colorectal polyps in a nationally representative sample., Methods: We analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample for 2000 through 2014. We included all adult patients who underwent elective colectomy or proctectomy and had a diagnosis of either nonmalignant colorectal polyp or colorectal cancer. We compared trends in surgery for nonmalignant colorectal polyps with surgery for colorectal cancer and calculated age, sex, race, region, and teaching status/bed-size-specific incidence rates of surgery for nonmalignant colorectal polyps., Results: From 2000 through 2014, there were 1,230,458 surgeries for nonmalignant colorectal polyps and colorectal cancer in the United States. Among those surgeries, 25% were performed for nonmalignant colorectal polyps. The incidence of surgery for nonmalignant colorectal polyps has increased significantly, from 5.9 in 2000 to 9.4 in 2014 per 100,000 adults (incidence rate difference, 3.56; 95% confidence interval 3.40-3.72), while the incidence of surgery for colorectal cancer has significantly decreased, from 31.5 to 24.7 surgeries per 100,000 adults (incidence rate difference, -6.80; 95% confidence interval -7.11 to -6.49). The incidence of surgery for nonmalignant colorectal polyps has been increasing among individuals age 20 to 79, in men and women and including all races and ethnicities., Conclusions: In an analysis of a large, nationally representative sample, we found that surgery for nonmalignant colorectal polyps is common and has significantly increased over the past 14 years., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)