Hamartomatous Polyposis Syndromes
Juvenile polyposis syndrome (JPS)
This syndrome affects approximately 1 in 100,000 people. At least one third of them have a family history of the disease, but approximately 25% are de novo mutations.
Endoscopically these polyps have a shiny, smooth surface that lacks the sulci-like appearance often noted in adenomas. On histological examination, large mucus-filled cystic chambers lined by stromal cells characterize these polyps.
Unlike the sporadic juvenile polyps (the most common form of polyp in the pediatric population, occurring in 2% of cases), polyps in JPS are more numerous and may affect the proximal gastrointestinal tract. The clinical diagnosis of JPS is made when a patient presents with: at least 3 to 10 colonic hamartomatous polyps (but they may present up to several hundreds over time); any extra-colonic hamartomatous polyps; or any hamartomatous polyps in a person with a known family history of JPS. Colorectal malignancy develops from adenomatous changes in the hamartomatous polyps and this confers a colon cancer risk approaching 60% over a lifetime.
Genetic testing and JPS
Germ-line mutations in the BMPR1A and the SMAD4 gene have been found to be responsible for approximately 25% and 15% of cases, respectively. A much smaller number are due to mutations in PTEN.
SMAD4 (18q21.1) is a member of the SMAD family of genes, which code for cytoplasmic mediators in the TGF b pathway, which mediates growth inhibitory signals. When TGF b or related ligands activate this pathway, serine-threonine receptors phosphorylate SMAD proteins allowing those to form a multi-protein complex with SMAD4 that translocates to the nucleus to bind several transcription factors and regulate the transcription of several genes. BMPR1A (10q22.3), bone morphogenic protein receptor, is a member of TGF b super-family and it is one of the serine-threonine receptors related with SMAD proteins.
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