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Rhabdoid Tumour Predisposition Syndrome (RTPS)

Rhabdoid tumour predisposition syndrome (RTPS) is a rare genetic condition that increases the risk of developing certain types of cancers, most commonly rhabdoid tumours. It is caused by genetic mutations in SMARCB1 and SMARCA4 tumour suppressor genes.

Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased risk of cancer as the result of inherited genetic mutations in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.

RTPS is generally diagnosed equally among the sexes, and are generally diagnosed before three years of age. However, anyone can develop this disease.

Types of Rhabdoid Tumour Predisposition Syndromes

There are two primary types of RTPS, which are classified based on the genetic mutation that causes the disease.

Rhabdoid Tumour Predisposition Syndrome Type 1 (RTPS1)

Rhabdoid tumour predisposition syndrome type 1 (RTPS1) is the most common subtype, and is caused by a mutation in the SMARCB1 gene. The most common tumour associated with this subtype is atypical teratoid/rhabdoid tumours (ATRTs) of the central nervous system, and has been associated with the development of peripheral nerve sheath tumours (most commonly schwannomas) and other tumours.

Rhabdoid Tumour Predisposition Syndrome Type 2 (RTPS2)

Rhabdoid tumour predisposition syndrome type 2 (RTPS2) is a less common subtype, and is caused by a mutation in the SMARCA4 gene. The most common tumour associated with this subtype is small cell carcinoma of the ovary – hypercalcemic type (SCCOHT), however it has also been associated with the development of ATRTs and other tumours.

RTPS is most commonly associated with the development of atypical teratoid rhabdoid tumours (ATRTs), however it has also been linked to other types of tumours. Some examples include:

  • Cribriform neuroepithelial tumours (CRINETs).

Treatment

When cancers are detected, they are staged and graded based on size, metastasis, and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you. However, each patient with RTPS will present with a unique disease behaviour, with varying tumour locations and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:

  • Type of tumours present.
  • Whether the tumours are malignant (cancerous) or benign (non-cancerous).
  • Tumour location.
  • Whether or not malignant tumours have metastasised.
  • Your age.
  • General health.
  • Your treatment preferences.

Your doctor may also recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.

 

Treatment options for tumours associated with RTPS may include:

  • Surgery to remove as much of the tumour(s) as possible – these will vary based on tumour type and location.
  • Chemotherapy.
  • Radiation therapy.
  • Immunotherapy.
  • Targeted therapy.
  • Watch and wait.
  • Clinical trials.
  • Palliative care.

Cancer Screening

Once a diagnosis of RTPS has been confirmed, implementing a targeted screening plan becomes essential due to the increased risk of developing certain cancers.  The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them.  Recommendations for RTPS may vary by age.

Birth to Eighteen Months Old

From birth to 18 months old, intensive surveillance may be recommended. The following may be required every 1-3 months:

  • Neurological examination.
  • Ultrasound of the abdomen, head and/or neck.
  • MRI of the brain and spine. Rarely, whole-body MRI might be required.

Nineteen Months Old to Five Years Old

The following may be recommended every three months:

  • Neurological examination.
  • Ultrasound of the abdomen, head and/or neck.
  • MRI of the brain and spine.

After Five Years Old

As the risk of RTPS dramatically decreases after this time, surveillance may be required less frequently and may include:

  • Physical and neurological examinations every six months.
  • Annual MRI of the whole body.
  • Abdominal and pelvic ultrasound every six months in individuals with small cell ovarian cancer.

Screening options for RTPS may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.

Risk factors

RTPS is caused by a genetic mutation in either the SMARCB1 or SMARCA4 tumour suppressor genes, which act to inhibit cell growth to prevent overproduction of cells and the development of tumours. It is an autosomal dominant disease, which means that you have a 50% chance of developing the condition if one of your parents carries the mutation.

Symptoms

The symptoms of RTPS often vary by the type(s) of tumours present. General symptoms of RTPS may include:

  • Abdominal mass.
  • Hypertension.
  • Haematuria.
  • Hypercalcaemia.
  • Difficulty urinating.
  • Difficulties with balancing and coordination and/or walking.
  • Slowed speech.
  • Headaches.
  • General weakness and fatigue.
  • Seizures.
  • Diplopia and/or other eye problems.
  • Nausea and/or vomiting.
  • Irritability.
  • Slowed growth.
  • Changes in eating habits.
  • Delayed developmental milestones, such as sitting up, walking and talking.
  • Abdominal bloating/swelling.
  • Abdominal/pelvic/lower back pain and/or pressure.
  • Unexplained weight loss/loss of appetite.
  • Fatigue.

Symptoms related to specific tumours can be found on our knowledgebase.

Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.

Diagnosis

If your doctor suspects you have tumours associated with RTPS, they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.

  • Physical examination.
  • Genetic testing.
  • Neurological examination.
  • Blood tests.
  • Urine tests.
  • Imaging tests, potentially including:
    • MRI (magnetic resonance imaging).
    • CT (computed tomography) scan.
    • PET (positron emission tomography) scan.
    • Ultrasound.
  • Exploratory surgery, such as an endoscopy.
  • Biopsy.

References

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