S6402 A Case of Juvenile Polyposis Syndrome Diagnosed by Genetic Testing Despite Hyperplastic Polyps and No Active Bleeding

Introduction: Juvenile polyposis syndrome (JPS) is an autosomal dominant disorder characterized by multiple hamartomatous polyps throughout the gastrointestinal tract, associated with an increased risk of colorectal and gastric malignancies. SMAD4 mutations are frequently implicated, often presenting with severe gastrointestinal (GI) bleeding, anemia, and hypoproteinemia. However, atypical presentations without overt bleeding may delay diagnosis. We present a case of JPS confirmed by genetic testing despite non-specific endoscopic and histologic findings. Case Description/Methods: A 36-year-old man with a year-long history of microcytic anemia presented with worsening fatigue, chest pain, frequent epistaxis, dizziness, and palpitations. Examination revealed pallor and dried nasal blood without active bleeding. Laboratory workup showed severe iron deficiency anemia (Hb 7.4 g/dL). He subsequently developed non-ST segment elevation myocardial infarction, requiring anticoagulation, which was complicated by GI bleeding. Endoscopic evaluation revealed multiple gastric, pyloric, duodenal, cecal, and colonic polyps, including a large duodenal lesion. Biopsies from multiple sites demonstrated hyperplastic polyps without dysplasia. Despite the inconclusive histology, genetic testing identified a pathogenic SMAD4 mutation, confirming JPS. Colorectal surgery planned a colectomy for the patient due to high polyp burden. Discussion: Diagnosis of JPS requires either multiple juvenile polyps in the GI tract or a pathogenic SMAD4/BMPR1A mutation, with 25% of cases occurring sporadically. This case underscores the importance of genetic testing, particularly when endoscopic and histologic findings are ambiguous and may mimic serrated polyposis syndrome (SPS). Unlike SPS, JPS surveillance begins earlier and includes cardiac screening due to associated hereditary hemorrhagic telangiectasia. Our patient’s iron deficiency anemia occurred without active GI bleeding, further complicating management due to iron intolerance. This case highlights the need for clear genotype-guided management strategies in JPS, including timing of surgical versus endoscopic interventions.