Turcot syndrome is a variant of familial adenomatous polyposis (FAP) that has the characteristics of FAP with additional tumours outside of the gastrointestinal tract, most notably colonthe longest portion of the large bowel that absorbs water and salts from ingested food and brain cancers. Like FAP, it is caused by an alteration in the adenomatous polyposis coli (APC) gene, which is a type of tumoura tissue mass that forms from groups of unhealthy cells suppressor gene, or in MLH1 and PMS2, which are mismatch repair genes.
Familial cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased riskthe possibility that something bad will happen 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.
Turcot syndrome is generally diagnosed equally among the sexes, and is often diagnosed before the age of 20. However, anyone can develop this disease.
Types of Turcot Syndrome
There are two primary types of Turcot syndrome that are classified by the genetic mutations causing the disease.
Type 1 Turcot Syndrome
Type 1 Turcot syndrome, also known as ‘true’ Turcot syndrome, is caused by mutations in the MLH1 gene or PMS2 gene, which are DNA mismatch repair genes (MMR). MMR genes are responsible for recognising and repairing errors in our DNA sequence that may occur during DNA replication. A mutation in any one of the MMR genes means that an error in the DNA sequence cannot be repaired, and may cause an accumulation of genetic mutations. This type of Turcot syndrome is an autosomal recessive disease, which means that both parents have to contribute a defective gene for you to develop it.
Type 2 Turcot Syndrome
Type 2 Turcot syndrome is caused by a mutation in the APC gene, which is a tumour suppressor gene. Tumour suppressor genes act to inhibit cell growth to prevent overproduction of cellsthe basic structural and functional unit of all living things 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 has the disease.
Turcot Syndrome Related Tumours
Turcot syndrome is most commonly associated with the development of colorectalrelating to the colon or rectum in the large bowel/intestine and brain tumours, however it has also been linked to other types of tumours. Some examples include:
The following tumours may also have an increased incidence in people with Turcot syndrome, however more research is needed to confirm:
- Pituitary adenomas.
- Ependymoma.
- Astrocytoma.
- Thyroid cancer.
- Adrenal gland tumours.
Treatment
When cancers are detected, they are staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you. However, each patient with Turcot syndrome 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 malignantcancerous, may grow and spread to other areas of the body (cancerous) or benignnot cancerous, can grow but will not spread to other body parts (non-cancerous).
- Tumour location.
- Whether or not malignant tumours have metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, 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 Turcot syndrome may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the tumour(s) as possible – these will vary based on tumour type and location.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Cancer Screening
Once a diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of Turcot syndrome has been confirmed, implementing a targeted screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer 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.
Because of how rare Turcot syndrome is, there hasn’t been any official screening recommendations made for this condition. Instead, your doctor will create a targeted screening program for you based on your individual circumstances.
Screening options for Turcot syndrome 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
Turcot syndrome is caused by mutations in any of the following genes:
- MLH1 (type 1 Turcot syndrome).
- PMS2 (type 1 Turcot syndrome).
- APC (type 2 Turcot syndrome).
The first two genes are known as mismatch repair (MMR) genes, and are known to cause type 1 Turcot syndrome. MMR genes are responsible for recognising and repairing errors in our DNA sequence that may occur during DNA replication. A mutation in any one of the MMR genes means that an error in the DNA sequence cannot be repaired, and may cause an accumulation of genetic mutations. This can predispose a person to cancer.
APC is a tumour suppressor gene, which acts to inhibit cell growth to prevent overproduction of cells and the development of tumours.
Symptoms
The symptoms of Turcot syndrome often vary by the type(s) of tumours present. General symptoms of Turcot syndrome may include:
- The presence of multiple polyps in the gastrointestinal tract.
- Café-au-lait spots on the skin.
- Anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection.
- Rectal bleeding.
- Diarrhoeafrequent discharge of watery or loose stools from the body.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Abdominal pain.
- Neurological symptoms, such as:
- Headaches.
- Changes in vision.
- Seizures.
- Difficulties with vision, hearing, and/or speaking.
- Difficulties walking and/or loss of balance.
- Unexplained loss of appetite/weight loss.
- Nauseato feel sick or likely to vomit and/or vomiting.
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 Turcot syndrome, 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 examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Genetic testing.
- Neurological examinationan assessment of sensory and motor functions, such as vision, balance and coordination.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- Exploratory procedures, potentially including:
- Colonoscopyan examination of the large intestine/bowel with a small, flexible instrument known as a colonoscope.
- Flexible sigmoidoscopyexamination of the lower portion of the large intestine and rectum with small, flexible instrument known as a sigmoidoscope .
- Other types of endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs as indicated.
- Biopsyremoval of a section of tissue to analyse for cancer cells.