"Juvenile Polyposis Syndrome" – What Is It?
Juvenile polyposis syndrome (JPS) is a disease caused by mutations, i.e., genetic changes in the BMPR1A or SMAD4 gene. It is characterized by the occurrence of polyps in the gastrointestinal tract and an increased risk of bowel and stomach cancer. In addition, mutations in the SMAD4 gene are associated with hereditary hemorrhagic telangiectasia (HHT), a vascular disease.
How Is "Juvenile Polyposis Syndrome" Diagnosed?
LFS can be diagnosed clinically based on classic diagnostic criteria. There are also personal and familial constellations in which it makes sense to arrange genetic testing for the presence of LFS. Such a genetic test and the detection of a TP53 mutation confirm the diagnosis of LFS.
Classic Diagnostics
Juvenile polyposis syndrome is suspected if the following findings are present:
- Lack of red blood cells, bleeding of the rectum, polyps emerging 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 one of the following findings:
- >5 juvenile polyps of the colon or rectum
- Multiple juvenile polyps of the upper and lower gastrointestinal tract
- Any number of juvenile polyps and juvenile polyposis in the family
- Presence of a SMAD4 or BMPR1A mutation
Genetic Diagnostics
The diagnosis of “juvenile polyposis syndrome” is confirmed by detecting a mutation, i.e., a genetic change in the SMAD4 or BMPR1A gene.
What Is the Risk of Cancer?
Polyps, Stomach and Bowel Cancer
Polyps occur in the upper and lower gastrointestinal tract and show significant variability in shape and size: flat-lying and pedunculated polyps can occur, ranging from a few to over 100 polyps. Juvenile polyps (where “juvenile” refers to the histology, not the age) can develop from infancy to adulthood. Most JPS patients have polyps by the age of 20. A complication can be bleeding and the resulting lack of red blood cells.
Most juvenile polyps are benign, but they can transform into malignant tumors. At the age of 35, 17%-22% of JPS patients are diagnosed with colorectal cancer (colon carcinoma); by the age of 60, this figure has risen to 68%. The average age at which colon cancer is diagnosed is 42 years. The probability of developing stomach cancer in JPS patients with polyps in the stomach is 21%.
Juvenile Polyposis Syndrome/Hereditary Hemorrhagic Telangiectasia (JPS/HHT Syndrome)
Patients with an SMAD4 mutation may develop JPS/HHT syndrome, which can show symptoms of both juvenile polyposis and HHT. HHT is a vascular disease and can manifest as nosebleeds, telangiectasias (vasodilatation of the capillaries of the skin), arteriovenous malformations (AVM, short-circuit connections between arteries and veins), or drumstick fingers. The clinical symptoms usually manifest in early childhood, with AVMs of the lungs and nosebleeds almost always occurring. Complications of JPS/HHT syndrome can include a lack of red blood cells, migraines, and headaches.
In addition, a SMAD4 mutation can lead to diseases of the aorta (main artery) close to the heart. These can include bulges, splittings of the aortic wall, or even widening of the entire vessel. Mitral valve malfunctions (heart valves between the left atrium and left ventricle) can also occur.
What Is Known About the Development of "Juvenile Polyposis Syndrome"?
Juvenile polyposis syndrome is caused by mutations, i.e., genetic changes in the BMPR1A or SMAD4 gene. These genes code for the BMPR1A or SMAD4 protein, both of which act as tumor suppressors to ensure that the development of tumor cells is suppressed.
If the BMPR1A or SMAD4 gene is present in an altered form, the corresponding proteins are no longer produced correctly and can, therefore, no longer function as tumor suppressors. This leads to the development of polyps and tumors.
Juvenile polyposis syndrome can be passed on from parents to their children. The inheritance is autosomal dominant. The remaining cases (around 67%) are due to a spontaneous or new mutation, known as a de novo mutation.
Is There Any Form of Treatment Available?
Removal of the polyps using gastroscopy or colonoscopy (endoscopic polypectomy) should be carried out as early as possible and can reduce the risk of malignant degeneration, bleeding, or intestinal obstruction. If there are 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 advisable.
JPS/HHT syndrome should be treated as a form of hereditary hemorrhagic telangiectasia that is not due to an SMAD4 mutation.
Diagnosis of " Juvenile Polyposis Syndrome" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " Juvenile Polyposis Syndrome" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
The aim is to detect developing complications early to achieve the best possible treatment results. To this end, regular medical check-ups are recommended by the following schedule (examination recommendations of the AACR 2016):
Patients with SMAD4 or BMPR1A Mutation or Clinically Diagnosed JPS:
- Annual examination and complete blood count, especially for intestinal bleeding, red blood cell deficiency, abdominal pain, constipation, diarrhea, or changes in stool shape, size, or color
- Colonoscopy and gastroscopy should be performed from the age of 15 or at the first symptoms
-
- If the result is negative, repeat in 3 years
- Remove the polyps (polyps ≥5mm) if there are only a few polyps. Screening should be continued annually until no additional polyps are found, then it can be extended to every 3 years.
- For many polyps: If necessary, partial or complete removal of the colon or stomach. Screening should be continued annually until no additional polyps are found, then it can be extended to every 3 years.
-
Additionally for Patients with SMAD4 Mutation
- Annual examination, especially about nosebleeds, other bleeding, shortness of breath, headaches, or neurological symptoms
- Regular blood tests (hematocrit, hemoglobin, and ferritin) and treatment of iron deficiency anemia, if necessary
- MRI of the head with visualization of the vessels in the first months of life. Repeat after puberty.
- Oxygen measurement by finger clip from early childhood every 1-2 years, CT of the lungs, or transthoracic echocardiography (heart ultrasound) in the event of abnormalities
- Regular screening for arteriovenous malformations of the lung after puberty, before a planned pregnancy, after pregnancy, and every 5 years with
- Contrast echocardiography (special cardiac ultrasound)
- CT of the lungs with contrast medium in the event of abnormalities in the contrast echocardiography performed previously
Juvenile Polyposis Syndrome- What You Can Do Yourself
You Should Pay Attention to This
People with this tendency to colorectal cancer should be treated at a center that offers early detection.
Regardless of the screening examinations, you should consult a doctor as soon as gastrointestinal tract symptoms occur. These can be blood or mucus discharge from the bowel, stool abnormalities such as diarrhea or constipation, flatulence, or pain. However, non-specific signs such as weight loss should also be noticed and reported to a doctor so that an investigation can be carried out to determine whether a stomach or colon cancer is present.
You should also consult a doctor if you have any other new abnormalities or complaints, e.g., nosebleeds, shortness of breath, headaches, or neurological symptoms.
Further Information
Unfortunately, we are not yet aware of any support groups for patients with juvenile polyposis syndrome. As soon as we have new information, we will add it here. However, patients can also register for the CPS registry at any time or have this done by the doctors looking after them.
Any further questions?
You can reach us by e-mail and telephone, or you can come to our consultation hours in person. For more information, please visit our contact page.
