IntroductionJuvenile Polyposis Syndrome (JPS) is a rare genetic disorder with a high risk of colorectal cancer, with an incidence rate ranging from 1 in 100,000 to 1 in 160,000. The lifetime risk of developing colorectal cancer in affected individuals can be as high as 39%–68%[1, 2]. Macroscopically, JPS is characterized by polypoid lesions that are pedunculated, exophytic, and smooth-surfaced, while histologically, the polyps are composed of dilated glands rich in mucus and accompanied by inflammatory cell infiltration [3]. According to the NCCN guidelines ”Genetic/Familial High-Risk Assessment: Colorectal,” individuals who meet at least one of the following criteria can be clinically diagnosed with JPS: (1) the presence of ≥5 juvenile polyps in the colon; (2) multiple juvenile polyps in the gastrointestinal tract; (3) at least one juvenile polyp in an individual with a family history of JPS [4]. Patients who meet the clinical diagnostic criteria for JPS typically carry pathogenic mutations in the BMPR1A or SMAD4 genes. SMAD4 is a key intracellular mediator of the transforming growth factor-β (TGF-β) superfamily signaling pathway [5], and the BMPR1A receptor is also a member of the TGF-β superfamily. Studies have shown that approximately 20% of JPS patients harbor pathogenic mutations in the coding regions of the BMPR1A or SMAD4 genes [6]. Currently, most clinical cases of JPS are associated with pathogenic mutations in either the BMPR1A or SMAD4 genes. Here, we report a novel de novo BMPR1A frameshift mutation (c.802_806delinsA; p.E268Tfs*14) in a three-generation JPS family and discuss its clinical implications. .