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Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM)

Familial atypical multiple mole melanoma (FAMMM) syndrome, also known as atypical mole syndrome, is a rare genetic condition characterised by the development of multiple moles (generally over 50) that look different from regular moles, as well as a family history of melanoma. It also increases the risk of developing certain types of cancer, most notably cutaneous melanoma.

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.

FAMMM tends to affect the sexes equally, and has a varying average age of diagnosis. Anyone can develop this disease.

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

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 FAMMM 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 FAMMM may include:

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

Cancer Screening

Once a diagnosis of FAMMM 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 FAMMM may include:

  • Annual skin examinations.
  • Annual physical examinations with family education surrounding signs and symptoms of related tumours and importance of prompt workup with imaging for any concerning symptoms.

Screening options for FAMMM 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

Risk factors for FAMMM include:

  • Having a genetic mutation in one of the following genes:
    • CDKN2A (cyclin-dependent kinase inhibitor 2A, tumour suppressor gene).
    • CDK4 (cyclin-dependent kinase 4, involved in DNA synthesis).
  • Having a close relative with the condition or with melanoma.

FAMMM is an autosomal dominant disease, which means that you have a 50% chance of developing the condition if one of your parents carries the genetic mutation.

Symptoms

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

  • A greater than average number of moles (generally over 50 moles).
  • Moles that are larger than normal (greater than 5mm diameter).
  • Moles that vary in colour and shape.
  • Moles that look abnormal when compared to a regular mole.

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

References

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