Turcot syndrome

Turcot syndrome is an autosomal dominant condition, this means that only one gene needs a change (mutation) in order for the person to be affected. People typically have two chromosomes, one from mom and one from dad. These chromosomes carry genes, which are the instructions for our body on how to work and grow. When a condition is autosomal dominant, like Turcot syndrome, then only one chromosome needs a genetic change to cause the condition. This means that each time a person has a child that child has a 50% (1 in 2) chance of inheriting the genetic change.

If you would like talk to someone more about how Turcot syndrome is passed on in a family talk with a genetic counselor. Genetic counselors near you can be found at the National Society of Genetic Counselors webpage.

If you have Turcot syndrome, you likely have other family members at-risk. It is likely you inherited the gene mutation from one of your parents. If a parent has the gene mutation, too, then your siblings are at-risk. They each had a 50% chance of inheriting the gene mutation and having Turcot syndrome. If you have children, then they each have a 50% chance of having the gene mutation. To find a genetic counselor near you who can discuss cancer testing, visit the National Society of Genetic Counselors Find a Genetic Counselor website.

Since screening can begin at a young age with this condition, a discussion with a genetics provider is recommended to determine the best time to perform genetic testing. Genetic testing for a hereditary cancer condition is an individual’s choice, and is an option available, but not mandatory, for other family members.

Turcot syndrome is a genetic condition that causes growths called polyps in the intestines and a higher chance of getting brain cancer and/or colon cancer. Turcot syndrome is considered an alternative form of two more common cancer syndromes associated with polyp formation- Lynch syndrome and familial adenomatous polyposis syndrome (FAP). Turcot syndrome is also referred to broadly as a mismatch repair deficiency syndrome. Mismatch repair is a process the body uses to repair damage to DNA. Damaged DNA can cause tumors to grow. Using mismatch repair corrects damage done to DNA to prevent a tumor from growing. Sometimes a mutation (change in DNA sequence) causes the parts of the mismatch repair system not to work, which means that it cannot fix other mutations. This leads to a higher chance of tumor development.

Turcot syndrome comes from having a mutation in one of the following genes: APC, MLH1, or PMS2. The APC gene is associated with a condition called familial adenomatous polyposis, and the MLH1 and PMS2 genes are associated with a different condition called Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC).

Mismatch repair is a process the body uses to repair damage to DNA. Damaged DNA can cause tumors to grow. Using mismatch repair corrects damage done to DNA to prevent a tumor from growing. Sometimes a mutation (change in DNA sequence) causes the parts of the mismatch repair system not to work, which means that it cannot fix other mutations. This leads to a higher chance of having a tumor grow.

Genes are made of a long series of chemicals called G, A, C, and T. The specific order of the letters determines what the gene makes. A change to the letters of a gene might change what it is supposed to make. A variant is a change in the letters of a gene where it is not known if that change causes a health condition or not. There might be some changes to the APC, MLH1, or PMS2 genes where it is possible that change causes a person to have Turcot syndrome, but it is not known for sure.

Lifetime cancer risks for people with Turcot syndrome are said to be similar to Lynch syndrome and familial adenomatous polyposis (FAP). Individuals with Lynch syndrome have about an 80% chance of having colon cancer in their lifetimes. They have about 1-3% chance of getting a brain tumor. People with FAP have a nearly 100% chance of having colon cancer in their lives. They have a less than 1% chance of getting a brain tumor.

The main characteristic for Turcot syndrome is the formation of adenomatous polyps (benign growths) in the gastrointestinal tract (also called colorectal). Signs and symptoms that polyps have formed can include, but are not limited to, diarrhea, rectal bleeding, fatigue, abdominal (stomach) pain, and weight loss. Turcot syndrome also has an increased risk for central nervous (brain) tumors which may cause symptoms depending on the size and location of the tumors. These symptoms may include, but are not limited to, headaches, vomiting, irritability, decreased vision, difficulty walking, clumsiness, jerky eye movements, weakness in the face, ringing in the ears, and double vision.

Turcot syndrome, familial adenomatous polyposis (FAP), and Gardner syndrome have many of the same symptoms and often times it is difficult to tell them apart.

FAP is diagnosed clinically when a person has (1) at least 100 colorectal (in the colon and rectum) adenomatous polyps, generally before 40 years old or (2) fewer than 100 adenomatous polyps and one relative with FAP. Other features that can be seen with FAP are duodenal (small intestine) adenomatous polyps, osteomas (non-cancerous bone tumor), dental abnormalities, congenital hypertrophy of the retinal pigment epithelium (spot in the back of the eye also called CHRPE), soft tissue tumors, and desmoid tumors.

Turcot syndrome has the colonic (in the colon) adenomatous polyps that are seen in FAP. However, Turcot syndrome also has central nervous system tumors; the most common tumors are called medulloblastoma and glioblastoma. Turcot syndrome has also been associated with mutations in the APC gene (which causes FAP) and in mismatch repair genes that are seen with Lynch syndrome (a different colorectal cancer syndrome).

Gardner syndrome also has the colonic (in the colon) adenomatous polyps seen in FAP. Gardner syndrome is also seen with osteomas (non-cancerous bone tumor) and soft tissue tumors. The most common types of soft tissue tumors seen are epidermoid cysts, fibromas, and desmoid tumors.

Both Turcot syndrome and Gardener syndrome are variations of FAP. However, anyone with a mutation in the APC gene is at risk for the tumors found in Turcot and Gardener syndrome.

Turcot syndrome is a predisposition to certain types of cancer, primarily colon and brain. Having Turcot syndrome gives a person a higher chance of developing cancer, but is not a certainty.

Different people with Turcot syndrome have different health problems, which is called variable expressivity. Not everybody who has a gene mutation causing Turcot syndrome actually gets sick. This is called incomplete penetrance.

As of the beginning of 2016, there are no clinical trials specific to Turcot syndrome. However, there are trials related to colon cancer and hereditary cancers that can be found on clinicaltrials.gov. Where it says "Search for Studies", enter "Turcot syndrome" or "colon cancer" or "hereditary cancer".

The treatment of Turcot syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment starts with screening for colon cancer. This involves having a colonoscopy on a regular basis. The frequency and starting age depends on the gene mutation. People with an APC gene mutation will likely start colonoscopies around the age of 10 and have one every one to two years. People with a MLH1 or PMS2 gene mutation will likely start colonoscopies in their early 20s, and have one every one to two years. If polyps are found, then a person might have surgery to remove the colon, or part of the colon. This is called a colectomy.

Individuals with Turcot syndrome can also consider periodic neurological screenings to test for the presence of a brain tumor. There are no specific guidelines for the frequency and method of screening for brain cancer. Individuals from families diagnosed with Turcot syndrome are encouraged to talk with a neurologist, a doctor who specializes in problems with the brain and central nervous system, about screening options.Treatment for brain tumors depends upon the type, size, and location of the tumor. It may include surgery to remove as much of the tumor as is possible without causing damage to the surrounding tissue. Surgery is often followed or accompanied by radiation and/or chemotherapy treatments.

Genetic counselors are experts in both genetics as well as the psychosocial implications of having a genetic condition. The genetic counselor will sit down with you and your family and go through the family history, discuss the diagnosis of Turcot syndrome, and help you work through what the diagnosis means for your family. Genetic counselors can help you talk with other family members about the diagnosis. Genetic counselors can also help you identify support resources available to you, and possibly even connect you with other families who are experiencing the same diagnosis. To learn more about genetic counselors and to find one near you visit the National Society of Genetic Counselors webpage.

Turcot syndrome can be causes by genes that are associated familial adenomatous polyposis (FAP) or Lynch syndrome. There are different screenings recommended for FAP and Lynch syndrome, your doctor may choose to follow one screening recommendation based on your symptoms, your family history, and what your genetic change is.

For FAP a prophylactic colectomy (removal of part or all of the colon) is be recommended to reduce the risk of colon cancer. Prior to the colectomy people with FAP should have a colonoscopy or sigmoidoscopy every 12 months starting at 10-15 years old. Once a person has a colectomy, and depending on the type of colectomy done, the recommended screening is an endoscopy every 6 months to 3 years, depending on polyps. For Lynch syndrome colonoscopies are recommended every 1-2 years starting at 20-25 years, or 2-5 years before the earliest colon cancer. For example if your father had colon cancer when he was 21 years old you would start colonoscopies at 16-19 years of age.

FAP also have increased risks for other types of cancer. The other recommended screenings are:

Turcot syndrome is a clinical variation (different type) of familial adenomatous polyposis (FAP) which has colorectal (in the colon and rectum) adenomatous polyps. 95% of people with FAP have polyps by 35 years of age. The number of polyps rapidly increase leading to colon cancer. Without a colectomy (surgical removal of all or part of the colon) a person with FAP will get colon cancer. If someone chooses not to get treated then the average age to be diagnosed with colon cancer is 39 years old; almost everyone who is not treated will develop colon cancer by 50 years of age. Turcot syndrome can also be cause by genetic changes in mismatch repair genes which cause Lynch syndrome (another genetic syndrome which increases the risk for cancer). With Lynch syndrome the lifetime risk for colorectal cancer is about 80%.

There is also an increased risk for central nervous system tumors, specifically medulloblastoma and glioblastoma. While the risk is significantly higher than the general population the total risk for developing a central nervous tumor is about 1-3%.

The genes related to Turcot syndrome are inherited in a dominant manner. This means that an individual only needs one mutation (change) in a gene in order to have an increased risk for the disease. If a parent has a mutation, there is a 50% chance that each of their children will inherit the mutation. If an individual has a mutation there is a 50% chance that their siblings also have the mutation. Men and women are equally likely to have these mutations and sons and daughters are equally likely to inherit them.

There are multiple ways to give to cancer research.

You can go to the American Cancer Society homepage (http://www.cancer.org/) and click on the orange "Donate" button on the top right part of the page.
You can go to the website for the Collaborative Group of the Americas on Inherited Colon Cancer (http://www.cgaicc.com/). One the right hand side of the page, near the bottom, you can click "Join Now!" to contribute and become a part of the community.

You can to the website for the Colorectal Cancer Coalition (http://fightcolorectalcancer.org/). One the top, hold your mouse over "Do Something". Then, click on "Fund the Fight". Towards the bottom of the page, there is a link to donate, as well as a link to shop in their store.

You can go to the website for the Colon Cancer Alliance (http://www.ccalliance.org/). Click on the large "Donate" button on the top right part of the page.

Turcot syndrome can be tested for using blood test. The test looks at the spelling of the three genes related to Turcot syndrome (called APC, PMS2, and MLH1). If the test finds any mutations (changes) in the genes that are known to cause Turcot syndrome, then you will be diagnosed with the condition. It is important to understand that even if a mutation is not identified in one of these genes, an individual may still be given a clinical diagnosis of Turcot syndrome if they have enough of the health problems associated with the condition.

To find a cancer genetic counselor near you who can discuss testing, visit the National Society of Genetic Counselors Find a Genetic Counselor website.

To find clinical research in Turcot syndrome, colon cancer, and hereditary cancers, go to https://clinicaltrials.gov/ct2/home. Where it says "Search for Studies", enter "Turcot syndrome" or "colon cancer" or "hereditary cancer".

Genetic testing is useful in distinguishing between APC-associated polyposis conditions (including Turcot syndrome, Gardner syndrome, and familial adenomatous polyposis (FAP)) and MUTYH-associated polyposis. This is important because APC-associated polyposis has additional tumor risks in addition to the colorectal (in the colon and rectum) adenomatous polyps. Also, APC and MUTYH-associated polyposis have different inheritance patterns; which can affect your family members’, including your children’s, risk for inheriting (getting) the same condition.

Additionally, Turcot syndrome has been caused by mutations in the APC gene and in mismatch repair genes (MLH1, MSH2, MSH6, and/or PMS2). When a mutation is found in the APC gene people tend to have a higher number of colorectal (in the colon and rectum) polyps and a higher risk for a central nervous tumor called medulloblastoma. Mutations in the mismatch repair genes increase the risk for a central nervous tumor called a glioblastoma multiform.

Knowing your mutation (genetic change) also allows for testing family members who have not had symptoms and/or genetic testing. If a mutation is found in you then your family members can be tested to see if they have the same mutation or not. If they do not have the same mutation then they are not at an increased risk for cancer compared to the general population.

If you have more questions about genetic testing talk with a genetic counselor. Genetic counselors near you can be found at the National Society of Genetic Counselors website.

Aside from cancer, Turcot syndrome is characterized by the formation of multiple benign growths (polyps) in the colon that occur in association with a primary brain tumor. These growths are associated with bleeding from the rectum, diarrhea, constipation, abdominal pain, and/or weight loss. The number and size of these polyps may vary greatly from case to case, ranging from fewer than 10 to more than 100.

Additional non-cancerous symptoms associated with Turcot syndrome include small, coffee-colored spots on the skin (cafe-au-lait spots), the formation of multiple, benign fatty tumors (lipomas), and/or the development of a type of skin cancer known as basal cell carcinoma. Basal cell carcinoma is characterized by the formation of small, shiny, firm masses of tissues (nodules); flat, scar-like lesions (plaques); or red patches covered by thick, dry, silvery scales on the skin.

The following list includes other symptoms of Turcot syndrome and the percentage of patients that experience them. Many of these symptoms are a direct result of a diagnosis of colon polyps/cancer or brain tumors, rather than a symptom of Turcot syndrome itself.

Support groups for people with Turcot syndrome and related hereditary colorectal cancer syndromes include:

Turcot syndrome is also known as Brain Tumor-Polyposis Syndrome 1 (BTPS1) or BTP1 Syndrome. Turcot syndrome is also referred to broadly as a mismatch repair deficiency syndrome. This is a category that includes other genetic syndromes. Turcot syndrome is considered an alternative form of two more common cancer syndromes associated with polyp formation- Lynch syndrome and familial adenomatous polyposis syndrome (FAP).

The American Cancer Society has resources for people affected by all types of cancer at http://www.cancer.org/.

Turcot syndrome is an intermediate form of two other colon cancer syndromes called Lynch syndrome and familial adenomatous polyposis syndrome (FAP). Both of those syndromes give a person a high chance of developing colorectal cancer, and increase the chances of having a brain tumor. Another similar condition is Gardner syndrome, which give a person a higher chance of having soft tissue tumors and polyps (growths) in the intestines.