What is juvenile polyposis syndrome?

What is Juvenile Polyposis Syndrome?

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by multiple hamartomatous polyps throughout the gastrointestinal tract, with a cumulative lifetime colorectal cancer risk of 39-68% and gastric cancer risk of 21% in those with gastric polyps. 1

Diagnostic Criteria

The diagnosis of JPS requires meeting any one of the following criteria:

• Five or more juvenile polyps in the colorectum 1
• Juvenile polyps throughout the gastrointestinal tract 2, 1
• Any number of juvenile polyps with a positive family history of JPS 2, 1

The term "juvenile polyp" refers to a specific histologic type, not the age at diagnosis. 2

Epidemiology and Genetics

• JPS occurs in approximately 1 per 100,000 newborns, making it about 10 times less common than familial adenomatous polyposis. 1
• Approximately 75% of cases have an autosomal dominant inheritance pattern with positive family history, while 25% are sporadic. 2, 3
• Germline mutations in SMAD4 (20%) or BMPR1A (20%) are identified in 40-60% of patients with JPS. 2, 4 Both genes are tumor suppressors in the TGF-β/BMP signaling pathway. 2, 4

Histopathologic Features

Juvenile polyps have distinctive microscopic characteristics that differentiate them from other polyp types:

• Hamartomatous architecture with dense, edematous stroma 1
• Cystic architecture with mucus-filled glands 2
• Prominent lamina propria with inflammatory cell infiltration 2
• Absence of smooth muscle core (unlike Peutz-Jeghers polyps) 2, 1

Clinical Presentation

Typical symptoms include:

• Rectal bleeding and anemia (most common presentation, occurring in 100% of pediatric cases) 1, 5
• Diarrhea 1
• Abdominal pain or intussusception 2, 1
• Protein-losing enteropathy 1
• Polyp numbers typically range from 50-200 in the colon. 1

Cancer Risk

• Cumulative lifetime colorectal cancer risk: 39-68%, with a relative risk of 34 compared to the general population 2, 1, 4
• Gastric cancer risk: 21% in those with gastric polyps 2, 1
• Cancer risk increases with age, though malignancy is rare during the pediatric period. 5
• Risk of cancers elsewhere in the gastrointestinal tract, including stomach, upper GI tract, and pancreas. 2

Associated Conditions

Critical distinction: SMAD4 mutations carry additional risk beyond JPS alone. 1

• Hereditary hemorrhagic telangiectasia (HHT)-JPS overlap syndrome occurs in patients with SMAD4 mutations, requiring cardiovascular surveillance for arteriovenous malformations in brain, lungs, liver, and other organs. 1, 6, 3
• Vascular anomalies (cardiac and CNS) occur in up to 30% of JPS patients. 2
• Extraintestinal features including valvular heart disease (11%), telangiectasia (9%, all in SMAD4 carriers), and macrocephaly (11%). 2

Management Strategy

Primary treatment consists of repeated endoscopic polypectomy at 2-year intervals for both colorectal and upper gastrointestinal polyps. 1, 6

Surveillance recommendations:

• Colonoscopy with polypectomy at 2-year intervals 1, 6
• Upper GI tract surveillance every 1-3 years starting at age 18 years 6
• Colectomy with ileorectal anastomosis is appropriate for patients with high polyp burden in the colon that cannot be managed endoscopically. 1, 6

For SMAD4 mutation carriers specifically:

• Mandatory screening for pulmonary AVMs using contrast echocardiography or chest CT 6
• MRI of brain to detect cerebral vascular malformations 6
• Doppler ultrasonography for hepatic involvement 6
• Avoid liver biopsy due to high hemorrhage risk 6

Critical Clinical Pitfalls

• Solitary juvenile polyps in children are common (most common polyps in childhood) and NOT associated with cancer risk, unlike syndromic juvenile polyposis. 2, 7 Any child with a juvenile polyp should be evaluated for JPS criteria.
• Patients with SMAD4 mutations may lack overt clinical symptoms of HHT but remain at risk of asymptomatic AVMs that can present suddenly with catastrophic complications. 6
• Failure to screen for HHT in SMAD4-positive JPS patients leads to missed life-threatening vascular malformations. 6
• Gastric polyps specifically confer a 21% gastric cancer risk, making upper GI surveillance critical and not optional. 1, 7