Juvenile polyposis syndrome

Juvenile polyposis syndrome (JPS) is a rare hereditary condition characterized by the development of multiple juvenile (hamartomatous) polyps in the gastrointestinal tract, most commonly in the colon and rectum, but also in the stomach and small intestine. The condition is typically diagnosed when a patient has five or more juvenile polyps in the colon, juvenile polyps throughout the gastrointestinal tract, or any number of juvenile polyps with a family history of juvenile polyposis. JPS should be distinguished from sporadic juvenile polyps, which are common and benign findings in children. The primary symptoms of JPS include rectal bleeding, anemia (due to chronic blood loss), abdominal pain, diarrhea, and rectal prolapse of polyps. In some cases, patients may experience protein-losing enteropathy, failure to thrive, or intussusception. A significant concern with JPS is the increased lifetime risk of gastrointestinal cancers, particularly colorectal cancer, with estimates ranging from 9% to 50%, and gastric cancer risk of up to 21%. Some patients may also develop hereditary hemorrhagic telangiectasia (HHT) overlap syndrome when the causative mutation is in the SMAD4 gene, which can lead to arteriovenous malformations in the lungs, brain, and liver. JPS is caused by pathogenic variants in the BMPR1A gene or the SMAD4 gene, both of which are involved in the transforming growth factor-beta (TGF-β) signaling pathway. Approximately 40-60% of patients have an identifiable mutation in one of these two genes. Management involves regular endoscopic surveillance with colonoscopy and upper endoscopy, typically beginning in the mid-teenage years or earlier if symptoms develop. Polyps are removed during surveillance to reduce cancer risk. In severe cases with numerous polyps that are difficult to manage endoscopically, surgical options such as colectomy may be necessary. Patients with SMAD4 mutations should also be screened for features of HHT, including pulmonary and cerebral arteriovenous malformations. Genetic counseling is recommended for affected individuals and their families.

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