SMAD4-related Familial Juvenile Polyposis Syndrome with Colon Cancer

Area of Science:

• Gastroenterology
• Genetics
• Oncology

Background:

• Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder.
• Characterized by hamartomatous polyps in the GI tract and increased cancer risk.
• SMAD4 germline mutations are found in approximately one-third of JPS cases.

Purpose of the Study:

• To describe the morphological and genetic aspects of two JPS cases within the same family.
• To investigate the clinical presentation of JPS with colon cancer.
• To highlight the role of SMAD4 mutations in JPS pathogenesis.

Main Methods:

• Morphological examination of polyps in both JPS cases.
• Genetic analysis for SMAD4 germline mutations.
• SMAD4 protein and DNA analysis in colonic adenocarcinoma.

Main Results:

• Both cases showed diffuse colorectal and gastric polyposis, including atypical polyps with dysplasia.
• Germline SMAD4 mutations were identified in both patients.
• Colonic adenocarcinoma revealed absent SMAD4 protein expression and loss of heterozygosity.

Conclusions:

• JPS associated with SMAD4 mutations exhibits unique polyp morphology, including extensive upper GI and gastric involvement.
• Morphological differences distinguish SMAD4-mutated JPS from non-mutated cases.
• SMAD4 genetic analysis aids JPS diagnosis and predicts malignancy risk via allele inactivation.