Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Juvenile Polyposis Syndrome (JPS) [D12.6]

OMIM numbers: 174900600993 (SMAD4)601299 (BMPR1A)

Dr. rer. nat. Karin Mayer

Scientific Background

Juvenile polyposis syndrome is a rare (incidence 1:16,000 to 1:100,000) autosomal dominant disease of the gastrointestinal tract (GI), characterized by juvenile (hamartomatous) polyps (> 5 in the colorectal region up to multiple polyps in the entire GI tract). 75% of all patients have a positive family history. Although most juvenile polyps are benign, 10-50% of all patients develop colorectal carcinomas, gastric carcinomas, tumors of the gastrointestinal tract or pancreatic carcinomas. Due to the increased tumor risk already during childhood and adolescence it is crucial to establish the diagnosis early and to carry out regular endoscopies.

In 20% of all patients, the molecular cause of the disease is a mutation in the SMAD4 gene or in the BMPR1A gene. SMAD4 (MADH4, DPC4 (deleted in pancreatic cancer)) is a tumor suppressor gene. The gene product plays a major role in the transforming growth factor-ß signal transduction. The BMPR1A (bone morphogenetic protein receptor 1A) gene encodes a type I serine/threonine kinase receptor of the TGFß super family. The BMP signal transduction is mediated from the surface receptor BMPR1A through SMAD4. A genotype-phenotype correlation between SMAD4 or BMPR1A mutations and the clinical signs and symptoms is very limited. The proportion of genomic deletions in both genes is up to 15%.

In predictive genetic testing, at-risk, asymptomatic individuals are tested, usually first-degree relatives of affected patients. According to the Genetic Diagnosis Act (GenDG) genetic counseling should be offered along with any genetic diagnostic procedure. In the case of predictive genetic testing, genetic counseling must be carried out prior to testing as well as after having received the result, unless there exists a written waiver of the at-risk person after having received written information on the content of the counseling.