Clinical characteristics: Juvenile polyposis syndrome (JPS) is characterized by predisposition to hamartomatous polyps in the gastrointestinal (GI) tract, specifically in the stomach, small intestine, colon, and rectum. The term "juvenile" refers to the type of polyp rather than to the age of onset of polyps. Most individuals with JPS have some polyps by age 20 years; some may have only four or five polyps over their lifetime, whereas others in the same family may have more than 100. If the polyps are left untreated, they may cause bleeding and anemia. Most juvenile polyps are benign; however, malignant transformation can occur. Risk for GI cancers ranges from 11% to 86%. Most of this increased risk is attributed to colon cancer, but cancers of the stomach, upper GI tract, and pancreas have also been reported. A combined syndrome of JPS and hereditary hemorrhagic telangiectasia (HHT) is present in most individuals with an SMAD4 pathogenic variant.

Diagnosis/testing: The diagnosis of JPS is established in a proband with any of the following: more than five juvenile polyps of the colorectum; multiple juvenile polyps throughout the GI tract; or any number of juvenile polyps and a family history of juvenile polyposis. Identification of a heterozygous pathogenic variant in SMAD4 or BMPR1A confirms the diagnosis if clinical features are inconclusive.

Management: Treatment of manifestations: Colonoscopy with endoscopic polypectomy to reduce the risk of cancer, bleeding, and intestinal obstruction. When a large number of polyps are present, removal of all or part of the colon or stomach may be necessary. Iron replacement and red blood cell transfusion as needed for anemia; treatment as needed for manifestations of HHT, arteriovenous malformations, aortopathy, and/or valvular disease per cardiologist and cardiothoracic surgeon.

Surveillance: Assess for rectal bleeding, anemia, abdominal pain, constipation, diarrhea, or change in stool size, shape, and/or color at each visit; complete blood count as needed based on symptoms; colonoscopy and upper endoscopy every three years beginning at age 15 years or earlier if symptomatic or if polyps were present on the prior colonoscopy. For individuals following surgical resection: endoscopic evaluation of the remaining colon, rectum, and ileal pouch. In individuals with (or at risk for) SMAD4-related JPS, follow HHT surveillance guidelines and consider transthoracic echocardiogram.

Evaluation of relatives at risk: It is appropriate to evaluate apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from early surveillance and intervention. Evaluations include molecular genetic testing (if the pathogenic variant in the family is known) and gastrointestinal and hematologic evaluations if the pathogenic variant in the family is not known.

Genetic counseling: JPS is inherited in an autosomal dominant manner. Up to half of individuals with JPS have an affected parent; approximately 50% of probands with JPS have no previous history of polyps in the family and may have the disorder as the result of a de novo pathogenic variant. Each child of an affected individual has a 50% chance of inheriting the pathogenic variant and developing JPS. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible if the pathogenic variant in the family is known.