What is Juvenile Polyposis Syndrome?
Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary condition characterized by multiple hamartomatous polyps throughout the gastrointestinal tract, with a lifetime colorectal cancer risk of 39-68% and gastric cancer risk of 21% in those with gastric polyps. 1, 2, 3
Definition and Diagnostic Criteria
JPS is clinically diagnosed when any of the following criteria are met: 1, 3
- Five or more juvenile polyps in the colorectum
- Juvenile polyps throughout the gastrointestinal tract (any number)
- Any number of juvenile polyps with a positive family history of JPS
The syndrome occurs in approximately 1 per 100,000 newborns, making it about 10 times less common than familial adenomatous polyposis. 1
Histopathologic Features
Juvenile polyps have distinctive microscopic characteristics that differentiate them from adenomatous polyps: 1, 3
- Hamartomatous architecture with dense, edematous stroma
- Cystically dilated glands filled with mucus
- Prominent lamina propria with inflammatory cell infiltration
- Absence of the smooth muscle branching pattern seen in Peutz-Jeghers polyps
Critical diagnostic pitfall: Large polyps often become lobulated and can develop adenomatous dysplasia, which may lead to misdiagnosis as familial adenomatous polyposis (FAP). 1, 4 Only 8.5% of JPS polyps contain mild-to-moderate dysplasia, and only 0.3% have severe dysplasia or cancer, so the diagnosis should not be based solely on the presence of dysplasia. 4
Genetic Basis
JPS is caused by germline mutations in genes involved in the BMP/TGF-beta signaling pathway: 1, 5, 3
- SMAD4/DPC4 on chromosome 18q (accounts for approximately 25-30% of cases)
- BMPR1A/ALK3 on chromosome 10q (accounts for approximately 25-30% of cases)
Approximately 50-60% of clinically diagnosed JPS patients have identifiable mutations in these genes. 3 About 75% of cases are inherited in an autosomal dominant pattern, while 25% are sporadic without family history. 5
Clinical Subtypes
JPS is classified into three phenotypic categories based on polyp distribution: 5
- Generalized juvenile polyposis (polyps throughout the GI tract)
- Juvenile polyposis coli (polyps limited to the colon)
- Juvenile polyposis of the stomach (specifically associated with SMAD4 mutations and carries the highest gastric cancer risk)
Cancer Risk and Associated Conditions
The cumulative lifetime colorectal cancer risk is 39-68%, with a relative risk of 34 compared to the general population. 2, 3 Patients with gastric polyps face a 21% risk of gastric cancer. 6
SMAD4 mutations carry additional risk: Patients with SMAD4 pathogenic variants may develop hereditary hemorrhagic telangiectasia-JPS complex, requiring cardiovascular surveillance for arteriovenous malformations. 6, 5
Clinical Presentation
Typical symptoms include: 1
- Rectal bleeding and anemia (most common)
- Diarrhea
- Abdominal pain
- Protein-losing enteropathy (in severe cases)
Polyp numbers typically range from 50-200 in the colon, though some patients have only a few polyps. 1 Polyps can occur in the stomach, small intestine, and colon. 1
Management Strategy
The primary treatment consists of repeated endoscopic polypectomy at 2-year intervals for both colorectal and upper gastrointestinal polyps. 1 This approach aims to reduce cancer risk and prevent symptoms such as bleeding, anemia, and diarrhea. 1
For patients with high polyp burden in the colon, colectomy with ileorectal anastomosis is appropriate. 1 This surgical option should be considered when endoscopic management becomes impractical due to polyp number or size. 1
Key Differential Diagnosis Considerations
Solitary juvenile polyps in children are common (occurring in 1-2% of children) and are NOT associated with cancer risk or JPS. 6 The presence of multiple polyps, family history, or extracolonic polyps distinguishes syndromic JPS from sporadic juvenile polyps.
JPS must be differentiated from: 1
- Peutz-Jeghers syndrome (distinctive smooth muscle branching pattern, mucocutaneous pigmentation, STK11 mutations)
- Familial adenomatous polyposis (adenomatous rather than hamartomatous histology, APC mutations)
- PTEN hamartoma tumor syndrome (PTEN mutations, macrocephaly, trichilemmomas)