What is juvenile polyposis syndrome?

Juvenile polyposis syndrome (JPS) is a disease caused by mutations – or genetic alterations – in the BMPR1A or SMAD4 gene. It is characterized by the occurrence of polyps in the gastrointestinal tract and an increased risk of colon and stomach cancer. In addition, mutations in the SMAD4 gene are also associated with hereditary hemorrhagic telangiectasia (HHT), a vascular disease.

How is juvenile polyposis syndrome diagnosed?

Classic Diagnostics

Juvenile polyposis syndrome is suspected with presentation of the following:

  • Anemia, rectal bleed, polyps protruding from the rectum

  • > 1 juvenile polyp (“juvenile” always refers to the histology of the polyps)

  • ≥ 1 juvenile polyp and JPS in the family

Diagnostic Criteria

The diagnosis of “juvenile polyposis syndrome” is confirmed by the presentation of one of the following:

  • > 5 juvenile polyps in the colon or rectum

  • Multiple juvenile polyps in the upper and lower gastrointestinal tract

  • Any number of juvenile polyps and juvenile polyposis in the family

  • The presence of a SMAD4 or BMPR1A mutation

Genetic Diagnostics

The diagnosis of “juvenile polyposis syndrome” is confirmed by detection of a mutation – or genetic alteration – in the SMAD4 or BMPR1A gene.

What is the risk of cancer?

Polyps, Stomach and Colon Cancer

Polyps occur in both the upper and lower gastrointestinal tract and exhibit a wide variety of shapes and sizes: Both flat and polyps that have a stalk occur, and their number ranges between only a few to over 100 polyps. Juvenile polyps (whereby “juvenile” refers to the histology and not the age of the patient) may develop from infancy to adulthood. Most JPS patients present with polyps by 20 years of age. Bleeding, which results in anemia, is a possible complication.

While most juvenile polyps are benign, they may progress to malignant tumors. By the age of 35, 17-22% of JPS patents suffer from colon cancer (colon carcinoma); and by the age of 60, 68% have colon cancer. The average age at diagnosis of colon carcinoma is 42. The probability of developing stomach cancer is 21% for JPS patients with polyps in the stomach.

Juvenile Polyposis Syndrome / Hereditary Hemorrhagic Telangiectasia (JPS/HHT Syndrome)

JPS/HHT syndrome can occur in patients with a SMAD4 mutation and can be associated with symptoms of juvenile polyposis and HHT. HHT is a vascular disease and can manifest as nose bleeds, telangiectasia (vascular dilation of the capillaries in the skin), arteriovenous malformations (AVM, short-circuit connections between arteries and veins), or drumstick fingers. The clinical symptoms usually appear during early childhood, with AVM of the lungs and nose bleeds almost always occurring. Complications of JPS/HHT syndrome may include anemia, migraines, and headaches.

Moreover, a SMAD4-mutation may be linked to diseases of the main artery, such as bulges or a split in the aortic wall or even the dilation of the entire vessel. In addition, it is also possible for malfunctions of the mitral valve (the heart valve between the left atrium and the left ventricle) to occur.

What causes juvenile polyposis syndrome?

Juvenile polyposis syndrome (JPS) is a disease caused by mutations – or genetic alterations – in the BMPR1A or SMAD4 gene. This gene encodes for the BMPR1A and SMAD4 proteins, both of which are tumor suppressors, meaning that they suppress the development of tumor cells.
Now if the BMPR1A or the SMAD4 gene is altered, the corresponding proteins will no longer be produced correctly, and consequently they will no longer be able to function normally as tumor suppressors. This leads to the development of polyps and tumors.

Juvenile polyposis syndrome can be passed on by parents to their children. In these cases, it is inherited as an autosomal dominant disease. The remaining cases (around 67%) are due to a spontaneous or new mutation, called a de novo mutation.

Is there a treatment?

The polyps should be removed as early as possible by gastroscopy or a colonoscopy (endoscopic polypectomy), which will reduce the risk of malignant progression, bleeding, and intestinal obstructions. If there is a large number of polyps or severe symptoms, partial or complete removal of the colon or stomach (total or subtotal colectomy or gastrectomy) may be recommended.

JPS/HHT syndrome should be treated in the same way as the hereditary form of hemorrhagic telangiectasia which is not associated with a SMAD4 mutation.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

Patients with an SMAD4 or BMPR1A mutation or clinically diagnosed JPS:

  • Annual examination and complete blood count, especially with regard to intestinal bleeding, anemia, abdominal pain, constipation, diarrhea, or changes in stool shape, size, or color

  • A colonoscopy and gastroscopy should be performed from the age of 15 or starting when symptoms initially appear.

    • If findings are negative: Repeat every 3 years.
    • If there are only a few polyps: Remove the polyps (polyps ≥ 5 mm). Screening should be continued every year until no additional polyps are detected, after which the interval can be extended to every 3 years.
    • If there are many polyps: If necessary, partial or complete removal of the colon or stomach. Screening should be continued every year until no additional polyps are detected, after which the interval can be extended to every 3 years.

Additionally for patients with an SMAD4 mutation:

  • Annual examination, especially with regard to nose bleeds, other bleeding, shortness of breath, headaches, or neurological symptoms

  • Regular blood tests, (hematocrit, hemoglobin, and ferritin) and treatment of any iron deficiency anemia

  • MRI of the head depicting the vessels in the first months of life, repeated after puberty

  • Oxygen measurement via a finger clip every 1-2 years starting in early childhood, with CT of the lungs or a transthoracic echocardiogram (heart ultrasound) if there are any anomalies

  • Regular screening for arteriovenous malformations of the lungs after puberty, before a planned pregnancy, after a pregnancy, and every 5 years with

    • Contrast echocardiography (special heart ultrasound)
    • CT of the lungs with contrast agent if there are any anomalies in the contrast echocardiography conducted beforehand

Self-Care and Support

What should I pay special attention to?

People with this tendency to develop colon cancer should be cared for at a center that provides surveillance screening.

Regardless of any surveillance examinations, you should see a doctor as soon as you develop symptoms of the gastrointestinal tract. These may present as blood or mucous in the stool, stool anomalies such as diarrhea or constipation, flatulence, or pain. Even non-specific signs such as weight loss should be noted and reported to a doctor so that he or she can check whether you have stomach or colon cancer.

You should also see a doctor right away if you notice any other newly occurring anomalies or symptoms, such as nose bleeds, shortness of breath, headaches, or neurological symptoms.

Support Groups and Additional Information

Unfortunately, we are as yet unaware of any existing support groups for patients with juvenile polyposis syndrome. We will add new information as it becomes available.