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DICER1 Syndrome

DICER1 syndrome (DICER1), also known as DICER1 tumour predisposition syndrome, is a rare genetic disorder that increases the risk of developing certain types of cancer, most commonly pleuropulmonary blastoma. It is caused by an alteration in the DICER gene, which is a type of tumour suppressor gene.

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.

DICER1 is generally diagnosed equally among the sexes, and is generally diagnosed before the age of 40. In many cases, it can be diagnosed in childhood and adolescence, however anyone can develop this disease.

DICER1 is most commonly associated with the development of pleuropulmonary blastoma, however it has also been linked to other types of tumours. Some examples include:

  • Central nervous system sarcomas (rare).
  • Benign tumours, potentially including:
    • Pulmonary cysts.
    • Cystic nephromas.
    • Hamartomatous polyps.

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 DICER1 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 DICER1 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.
  • Clinical trials.
  • Palliative care.

Cancer Screening

Once a diagnosis of DICER1 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.  Some recommendations for DICER1 may include:

  • Annual physical examinations with family education surrounding signs and symptoms of disease and importance of prompt workup with imaging for any concerning symptoms.
  • Chest x-rays every 4-6 months until eight years old, then annually until age 12.
  • Annual physical thyroid examination.
  • Thyroid ultrasounds every 3-5 years.
  • Pelvic ultrasound every 6-12 months for females beginning by age eight until at least 40 years old.
  • Abdominal ultrasound every six months until eight years old, then annually until age 12.
  • Annual eye examinations from age three until at least age 10.

Screening options for DICER1 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

DICER1 is caused by a genetic mutation in the DICER tumour suppressor gene, which acts 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 DICER1 often vary by the type(s) of tumours present. General symptoms of DICER1 may include:

  • Dyspnea.
  • Unexplained weight loss/loss of appetite.
  • Fevers.
  • Abdominal pain.
  • Abdominal distention.
  • Abdominal mass.
  • Menstrual irregularities.
  • Amenorrhoea.
  • Precocious (early) puberty.
  • Changes in vision, most commonly decreased vision.
  • Headaches.

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 DICER1 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.
  • Neurological examination.
  • Pelvic examination.
  • Genetic testing.
  • Blood tests.
  • Urine tests.
  • Imaging tests, potentially including:
    • Chest x-ray.
    • Ultrasound.
    • MRI (magnetic resonance imaging).
    • CT (computed tomography) scan.
    • PET (positron emission tomography) scan.
  • Exploratory procedures, such as an endoscopy.
  • Biopsy.

References

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