Juvenile Polyposis coli - BMPR1A, SMAD4, ENG

BMPR1A, SMAD4, ENG

Clinical Features

The term Juvenile Polyposis coli (JPS) refers less to the age of the patient as to the histology regarding the development of hamartomatous polyps in the gastrointestinal tract, where the stomach, small intestine, colon and rectum may be affected. The course of the disease can vary greatly; it can occur in childhood in a myriad of polyps or manifest itself in adulthood with a low number of individual polyps. On average, most affected patients over the age of 20 develop at least some polyps.

If polyps remain undetected, bleeding can occur, often resulting in anaemia, hypoproteinanaemia and a corresponding developmental delay.

Juvenile Polyposis coli is categorized as essentially benign, but a series of independent studies has shown an eventual 9-50% risk of developing cancer. The literature indicates this is frequently the result of an adenomatous transformation of polyps which, in turn, become adenocarcinoma. Although the highest risk of cancer remains in the large intestine, carcinoma can also occur in the upper gastrointestinal tract and pancreas. Treatment is normally non-invasive; only rare cases require surgery. Preventative measures should take the entire gastrointestinal tract into consideration.

Diagnostic criteria for Juvenile Polyposis coli

more than 5 juvenile polyps in the colorectum, or
multiple juvenile polyps in the entire gastrointestinal tract, or one or less than 5 juvenile polyps in combination with an affected family member

Genetic Information

In approximately 50% of cases, a disease-causing genetic mutation has been detected. Most patients are carriers of mutations in either the SMAD4 gene (20%) or the BMPR1A gene (20%) .

The SMAD4 gene belongs to the TGF-beta signaling pathway, the BMPR1A gene to the BMP signal pathway (which is very homologous to the TGF-beta pathway). In rare cases, mutations are found in the ENG gene (Endoglin gene), which also belongs to the TGF-beta signaling pathway and normally exhibits germline mutations in case of hereditary hemorrhagic telangiectasia (HHT).

In contrast to JPS patients with BMPR1A mutations or patients with no detected mutations, patients with SMAD4 mutations have a higher number of juvenile polyps and an increased risk of developing tumors as a result of adenomatous transformation. In these cases, the upper gastrointestinal tract is notably affected.