What are the other Names for this Condition? (Also known as/Synonyms)

• Brain Tumor-Polyposis Syndrome
• Glioma-Polyposis Syndrome
• Mismatch Repair Cancer Syndrome (MMRCS)

What is Turcot Syndrome? (Definition/Background Information)

• Turcot Syndrome is a rare genetic disorder that is characterized by non-cancerous growths (or polyps) in the gastrointestinal tract. Even though the polyps may be initially benign, some tumors may transform into cancer over time. Also, the number of polyps in the colon may increase with time
• Primary tumors can also occur in the brain simultaneously. The types of brain tumor commonly observed in Turcot Syndrome are glioblastoma and medulloblastoma
• Mutations in APC, MLH1 or PMS2 genes are known to cause Turcot Syndrome. The disorder may either be inherited in an autosomal recessive or autosomal dominant manner
• The symptoms of the condition may include formation of benign liver nodules, anemia, diarrhea, rectal bleeding, and fatigue. Changes in skin, in the form of coffee-colored spots, sebaceous cysts, and basal cell carcinoma may also occur. Additionally, brain tumors may give rise to headaches, vision abnormalities, balance issues and seizures
• The diagnosis of Turcot Syndrome is made on the basis of imaging studies for detecting tumors, and blood tests to check for mutation(s) in the genes that are known to cause the condition
• Treatment methods are aimed at providing relief from symptoms, preventing tumor growth, and minimizing complications, such as polyp bleeding and tumors becoming malignant
• Being an inherited condition, presently there is no cure for Turcot Syndrome. Also, without proper diagnosis and treatment, the life expectancy can be affected. If colon cancer or brain tumors develop, the prognosis may be guarded

Who gets Turcot Syndrome? (Age and Sex Distribution)

• Turcot Syndrome is a very rare genetic disorder. Thus far, only about 150 cases have been reported in the medical literature from various parts of the world
• The age of symptom-onset may vary, ranging from childhood to adulthood
• Both genders may be affected by this disorder

What are the Risk Factors for Turcot Syndrome? (Predisposing Factors)

The risk factors for Turcot Syndrome may include:

• Presence of inherited genetic mutations in APC gene or in mismatch repair genes (MLH1 and PMS2)
• Family history of colorectal cancer or brain tumors, especially among parents, brothers, or sisters

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Turcot Syndrome? (Etiology)

Turcot Syndrome is caused by mutation(s) in the APC, MLH1, or PMS2 genes. Based on the gene mutation causing the condition and the mode of inheritance, the disorder is classified into Type 1 and Type 2 types.

Type 1 Turcot Syndrome:

• Mutation(s) in MLH1 or PMS2 genes cause this syndrome type. This type is also known as “true” Turcot Syndrome
• MLH1 and PMS2 are located in the short arm of chromosome 3 and 7, respectively. These genes belong to the DNA mismatch repair (MMR) genes family
• Under normal circumstances, the MLH1 and PMS2 genes code for proteins that interact to form a protein complex and repair mistakes in DNA replication
• When either gene is mutated, the resultant protein is non-functional, which compromises the DNA repair mechanism
• This results in an accumulation of DNA with errors, inside the cells, leading to cellular malfunction and subsequent tumor formation in the colon and brain
• The gene mutations in type 1 Turcot Syndrome are known to cause a specific kind of brain tumors known as glioblastoma
• The MLH1 and PMS2 mutations are inherited in an autosomal recessive manner: In this type of inheritance, an individual must possess both copies of a causative gene in the defective form in each cell of his/her body for the condition to manifest itself. The affected individual typically inherits a single defective copy of the gene from each unaffected parent

Type 2 Turcot Syndrome:

• Mutation(s) in the APC gene causes this type of Turcot Syndrome; this gene localizes to the long arm of chromosome 5
• The APC gene codes for the adenomatous polyposis coli (APC) protein, which is a tumor suppressor (i.e., such proteins regulate the proliferation of cells)
• Under normal circumstances, the APC protein interacts with other proteins to bring about normal cell division, cell-cell association, movement of cells within a tissue, maintenance of chromosome numbers during cell division, and cessation of cell proliferation
• When the APC gene is mutated, the resultant protein may be truncated and non-functional, and is hence, unable to interact with other proteins and regulate cell division
• The abnormal multiplication of cells, lead to the formation of polyps in the colon and tumors in the brain (typically medulloblastomas)
• Mutation(s) in APC gene are inherited in an autosomal dominant manner: In this type of inheritance, a single defective copy of the causative gene in every cell of an individual is sufficient to cause the condition. The affected individual inherits the disorder from an affected parent

What are the Signs and Symptoms of Turcot Syndrome?

The signs and symptoms of Turcot Syndrome may involve the colon, brain, and other organs in the body, and can vary between affected individuals in type and severity. The following are some common signs and symptoms: 

• Growths (polyps) in the mucus layer of the colon, which may range in numbers from a few to over 100
• Anemia
• Change in bowel habits; bleeding from the rectum
• Diarrhea
• Tiring easily, fatigue
• Abdominal pain 
• Unexplained weight loss
• Liver nodules due to hepatic focal nodular hyperplasia (a benign tumor of the liver)
• Neurological symptoms due to brain tumors, which may include:
  • Headache
  • Blurred vision
  • Loss of balance
  • Seizures 
• Changes in skin may be observed, such as:
  • Cafe-au-lait spots (coffee-brown colored spots)
  • Sebaceous cysts
  • Basal cell carcinomas (which may be characterized by shiny mass of cells, plaques, or red patches with dry, thick and silvery scales)

How is Turcot Syndrome Diagnosed?

The diagnosis of Turcot Syndrome is made with the help of the following tools:

• A thorough physical examination and an assessment of symptoms
• An evaluation of family medical history
• Sigmoidoscopy: It is a diagnostic method to view the last 1/3rd of the colon (known as the sigmoid colon) and the rectum, in order to check for abnormalities such as polyps. A flexible tube with a light and a camera is inserted through the anus for this procedure
• Screening colonoscopy to determine the presence of multiple polyps, if any
• Fecal occult blood test (FOBT) to check for blood in stool, which may be indicative of colon cancer, requiring further tests
• Double contrast barium enema radiography: X-rays of the colon and rectum with two contrast forms, to detect the presence of masses, if any
• Blood tests to check for mutation(s) in the APC, MLH1, or PMS2 genes 
• CT and MRI scans of brain to check for tumors

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Turcot Syndrome?

The following are some potential complications that may develop in individuals with Turcot Syndrome:

• Bleeding of polyps
• Transformation of a benign colon polyp to cancer
• Brain tumors may severely affect the quality of one’s life, owing to vision and balance issues
• Seizures

How is Turcot Syndrome Treated?

The treatment methods for Turcot Syndrome aim at providing relief from symptoms, arresting the growth of tumors, and minimizing complications. The following are some treatments available for the disorder:

• A prophylactic removal of colon (called prophylactic colectomy) to help decrease the chances of developing colon cancer
• Proctocolectomy or the removal of colon and rectum
• Ileostomy procedure: This may be required in individuals whose polyps are growing aggressively. In this surgery, a part of the small intestine known as the ileum is attached to an opening created in the abdominal wall
• Ileoproctostomy procedure: In this procedure, the large intestine is removed and the small intestine is attached to the rectum
• Ileoanal anastomosis procedure; wherein the small intestine is directly attached to the rectum following removal of the large intestine
• Complete excision of basal cell carcinomas of skin through surgery
• Brain tumors, including astrocytoma, glioblastoma, and medulloblastoma, may be resected through surgical interventions, with follow-up chemotherapy
• Chemotherapy and/or radiation depending on the clinical situation
• Medications, such as non-steroidal anti-inflammatory drugs (NSAIDs including Celecoxib and Sulindac), to decrease the number and size of the polyps

How can Turcot Syndrome be Prevented?

At the present time, there are no methods or guidelines available for the prevention of Turcot Syndrome, since it is a highly uncommon genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in better understanding of the risks during pregnancy
• If there is a family history of the condition, then genetic counseling may help couples assess risks while planning for a child
• At risk family members who have not yet been genetically tested are strongly recommended to undergo annual colonoscopy
• Active research to explore treatment and prevention options for inherited disorders, such as Turcot Syndrome, is currently being conducted

Regular medical screening at periodic intervals with tests and physical examinations are strongly recommended.

What is the Prognosis of Turcot Syndrome? (Outcomes/Resolutions)

The prognosis of Turcot Syndrome depends on the severity of the symptoms, the overall health status of the affected individual, and his/her response to treatment.

• Without medical intervention, the median life expectancy may be shortened
• Fatalities usually occur due to malignant brain tumors or from colorectal cancer
• According to one study, the following were noted:
  • Mean survival rate of 5.6 years for those diagnosed with medulloblastoma and colonic adenomas
  • Mean survival rate of 2.3 years for those diagnosed with glioblastoma and adenomas

Additional and Relevant Useful Information for Turcot Syndrome:

• Turcot Syndrome is also known by the following synonyms
  • Mismatch repair deficiency (MMR deficiency)
  • Central nervous system (CNS) tumors with familial polyposis of the colon
  • Malignant tumors of the central nervous system associated with familial polyposis of the colon
• The genetic defect in type 1 Turcot Syndrome is similar to hereditary non-polyposis colorectal cancer (HNPCC). This type of cancer can develop from a few polyps, or even in their absence
• Type 2 Turcot Syndrome is associated with familial adenomatous polyposis (FAP)
• Turcot Syndrome is also considered an unusual variant of Lynch syndrome. This inherited cancer risk is caused by mutation(s) in DNA mismatch repair genes, including MLH1 and PMS2. Although individuals with Lynch syndrome bear an increased risk of cancers in the gastrointestinal tract, tumors of the brain are not common (that are associated with Turcot Syndrome)