Muir-Torre syndrome

The standard in cancer genetic testing is to test someone in the family who has had cancer first. However, if no one with cancer is available, testing an individual without cancer may also be appropriate. If an individual has a mutation, there is a 50% chance that their first-degree relatives (parents, siblings and children) would have the same mutation. The risk for other family members is less, depending on their relationship with the affected person, but still significant. In general, children should not be tested until they are at least 18 years of age. Genetic testing for a hereditary cancer condition is an individual decision and not all family members may wish to be tested. Genetic counseling is recommended for all family members to discuss the benefits and limitations of testing.

Your local hospital or genetic counselor may be able to connect you with other individuals in your area with Muir-Torre or Lynch syndrome.

Other individuals with Muir-Torre syndrome can also be found at the following resources:

To determine if you are someone who would be a good candidate for genetic testing, meeting with a genetics provider is recommended. You can find a genetic counselor near you at [link url="” target=”_blank”>www.findageneticcounselor.org or [link url="” target=”_blank”>www.cancer.gov/cancertopics/genetics/directory.

For Lynch syndrome/Muir-Torre syndrome there are typically two types of tumor tests that can be done. One is called microsatellite instability (MSI) testing. The microsatellite is a repeat of letters at the end of the gene, and there are supposed to be a certain number of repeats for the gene to function properly. Sometimes, there can be too many or too few repeats, and if this happens it is said to be MSI- high, which makes the doctors more suspicious that this may be Muir-Torre or Lynch syndrome. Another type of tumor test that can be done is called immunohistochemistry or IHC staining. This type of tumor testing is looking at the proteins. Genes give the body instructions for how to make proteins, and the IHC testing is looking to see if there are any proteins missing. If a protein is missing that may suggest that the gene that makes that protein may also be missing. IHC testing can give doctors and genetics health care providers an idea of which genes they should begin with for genetic testing.

The MLH1 and MSH2 genes are called mismatch repair genes. These genes are the instructions for building proteins that are help to repair our genetic information, or DNA, if there is any damage. If there is a change, or mutation, in the MLH1 or MSH2 genes, the proteins are not built correctly and they are not able to repair the damaged DNA. When damaged DNA cannot be repaired, the damage can contribute to the chance that a cancer will develop.

Individuals with Muir-Torre syndrome who have not had cancer may see a gastroenterologist ("GI doctor") to help manage the colonoscopy and the upper endoscopy screening and females may see a gynecologist or gynecologic oncologist who specializes in cancer of the female organs regarding uterine and ovarian cancer prevention. A genetic counselor may also be involved in care to manage the screening and prevention options and to work with the family as a whole. Individuals who have had cancer related to Muir-Torre will typically have a surgeon, oncologist (a cancer doctor) and possibly a radiation oncologist (a cancer doctor who treats with radiation therapy).

Individuals who have inherited a genetic change in the MLH1 or MSH2 gene and have Muir-Torre syndrome have a 52-82% risk of developing colon cancer and a 6-13% risk of developing stomach cancer by age 70. Women have a 25-60% risk of developing uterine cancer and a 4-24% risk of developing ovarian cancer by age 70. The risk for other cancers is smaller but still increased above the risk of someone in the general population. The risk for the skin tumors associated with Muir-Torre syndrome is 1-9%.

You should discuss your specific prep recommendations with your doctor who will give you more specific and detailed instructions. The goal of the prep is to get your colon as clean as possible before the examination. In general, the prep consists of: drinking clear liquids only 24 hours before the exam, not eating solid foods, and drinking a large amount of a special cleansing solution and/or special oral laxatives recommended by your doctor.

The average age of uterine cancer in individuals with Muir-Torre syndrome is between 48-62 years old. However, not everyone with Muir-Torre syndrome will develop uterine cancer.

The average age of colon cancer in individuals with Muir-Torre syndrome is between 44-61 years old. However, not everyone with Muir-Torre syndrome will develop colon cancer.

Muir-Torre syndrome is a part of a family of hereditary cancer conditions. The most common of these is called Lynch syndrome, which causes an increased risk for colon, uterine, ovarian, small intestinal, biliary tract, and pancreatic cancer. People with Muir-Torre syndrome have increased risks for these cancer and also have skin tumors. The skin tumors associated with this condition include sebaceous gland tumors (tumors that occur in the glands that produce an oily substance called sebum) and keratocanthomas of the skin (rapidly growing tumors that occur usually on sun-exposed areas of the skin).

Symptoms of colon cancer may include: a change in bowel habits including constipation, diarrhea, or narrowing of the stool, which lasts for more than a few days, feeling that you need to have a bowel movement but the feeling is not relieved by doing so, blood in the stool, rectal bleeding, cramping or abdominal pain, weakness, fatigue, and unintended weight loss.

Symptoms of uterine cancer may include: abnormal vaginal bleeding (which can range from a watery and blood-streaked flow to a flow that contains more blood), vaginal bleeding during or after menopause, vaginal bleeding between periods, non-bloody vaginal discharge, and pain in the pelvic region.

Lynch syndrome/Muir-Torre syndrome should be considered whenever an individual has a personal or family history of the following:

Changes, or variants, in the MLH1 or MSH2 genes can cause Muir-Torre syndrome and result in an increased risk for colon cancer, uterine cancer, ovarian cancer, stomach cancer, and other skin tumors. Changes in the MLH2 gene are more common in people who have Muir-Torre syndrome than changes in the MSH1 gene.

Muir-Torre syndrome is inherited as an autosomal dominant condition. This means that only one change is necessary to cause this increased cancer risk. These genetic changes are typically inherited from parent to child. However, Muir-Torre syndrome does have reduced penetrance, which means that not everyone that has a significant change in these genes will develop cancer or the skin findings. As a result, many, but not all, people who have Muir-Torre syndrome will have a family history of cancer.

Not everyone who has a personal or family history of the symptoms of Muir-Torre syndrome will test positive for a change, or mutation, in the MLH1 or MSH2 genes. This suggests that other genes may cause Muir-Torre syndrome but have not yet been discovered.

A gastroenterologist will use an endoscope (a small tubing that has a tiny camera attached to the end) to go down through the esophagus into the stomach and the first part of the small intestine. This is used to look for any polyps located in the small intestine, stomach, or esophagus.

A variant is a change in the DNA when compared to a standard reference. A variant may or may not cause a higher risk for disease depending on the type of variant, the location and how it might change a protein.

A variant is a change in the DNA when compared to a standard reference. A variant may or may not cause a higher risk for disease depending on the type of variant, the location and how it might change a protein.

Muir-Torre is a variation of Lynch syndrome. Individuals with Muir-Torre have specific types of skin tumors in addition to the cancers that are often seen in people with Lynch syndrome. The types of cancer that are suggestive of Muir-Torre syndrome include: colon cancer, uterine cancer, ovarian cancer, stomach cancer, biliary tract cancer, small intestinal cancer, pancreatic cancer, and brain cancer. The skin tumors associated with Muir-Torre include sebaceous gland tumors (tumors that occur in the glands that produce an oily substance called sebum) and keratocanthomas (rapidly growing tumors that occur usually on sun-exposed areas of the skin).

Sebaceous gland tumors typically appear as a single small bump on the face, scalp, chest, back or stomach. Keratocanthomas can occur on many parts of the body and are typically fast-growing, red and dome-shaped with an indentation in the center. These skin findings can be very similar to other skin bumps so they are typically a concern mainly if seen with a personal or family history of cancer.

Symptoms of colon cancer may include: a change in bowel habits including constipation, diarrhea, or narrowing of the stool, which lasts for more than a few days, feeling that you need to have a bowel movement but the feeling is not relieved by doing so, blood in the stool, rectal bleeding, cramping or abdominal pain, weakness, fatigue, and unintended weight loss.

Symptoms of uterine cancer may include: abnormal vaginal bleeding (which can range from a watery and blood-streaked flow to a flow that contains more blood), vaginal bleeding during or after menopause, vaginal bleeding between periods, non-bloody vaginal discharge, and pain in the pelvic region.

Some individuals with Muir-Torre syndrome can develop cancer at any age, which is known as a variable age of onset. This is seen both within the same family and in different families. Different individuals may develop different types of cancer or skin tumors associated with Muir-Torre syndrome, and this is known as variable expression. Individuals who have a change, or mutation, in the MLH1 or MSH2 gene may never develop cancer or skin tumors, which is referred to as reduced penetrance.

Testing for Muir-Torre syndrome is not typically offered to individuals under the age of 18. Newborn screening, which specifically looks at specific genetic disorders in most newborns, does not include screening for Muir-Torre.

There are different options for genetic testing and meeting with a genetics health provider can help determine which option of genetic testing makes the most sense for you based on your personal or family history. An individual may be tested for the MLH1 and MSH2 genes alone or along with multiple other genes that can also cause an increased risk for cancer, including the other genes associated with Lynch syndrome – MSH6, PMS2, and EPCAM. Testing multiple genes at once is called a cancer panel. Additionally, If a family member has already been identified as carrying a specific disease-causing change, it may be appropriate just to test for that specific change.

Muir-Torre syndrome can be abbreviated as MTS.

Your doctor should also be aware of the increased cancer risk and symptoms of the cancers and tumors that can be caused by Muir-Torre syndrome.

Symptoms of colon cancer may include: a change in bowel habits including constipation, diarrhea, or narrowing of the stool, which lasts for more than a few days, feeling that you need to have a bowel movement but the feeling is not relieved by doing so, blood in the stool, rectal bleeding, cramping or abdominal pain, weakness, fatigue, and unintended weight loss.

Symptoms of uterine cancer may include: abnormal vaginal bleeding (which can range from a watery and blood-streaked flow to a flow that contains more blood), vaginal bleeding during or after menopause, vaginal bleeding between periods, non-bloody vaginal discharge, and pain in the pelvic region.

Your doctor should be aware of the Lynch syndrome/Muir-Torre cancer screening recommendations, which can be found on the NCCN website. These recommendations include:

Each pregnancy or child of an individual with Muir-Torre syndrome will have a 50% chance of inheriting the same condition. If there is a concern about passing that genetic risk on, there are a couple options for family planning. One option is to adopt or use a sperm or egg donor instead of the genetic material from the parent with the condition. Another option is to have biological children, and know that there is a 50% risk that each child could inherit this mutation. A final option, if you know the gene change causing Muir-Torre syndrome in your family, is having in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD). Through the process of PGD, embryos can be checked to see if they contain the MLH1 or MSH2 mutation in the family or not, and only embryos that do not contain the mutation will be implanted in the mother.

The colonoscopy procedure depends on your case and your doctor. Your doctor can give you a better idea in your exact situation. The average procedure takes approximately 30 minutes, and you will be in the recovery room afterwards for another 30 minutes.

Muir-Torre syndrome is inherited in an autosomal dominant manner. This means that an individual only needs one copy of a disease-causing genetic change (mutation) to have the disease and an increased risk for skin tumors and cancers. If an individual has a mutation, there is a 50% chance that their first-degree relatives (parents, siblings and children) would have the same mutation. The risk for other family members is less, depending on their relationship with the affected person, but still significant.

You can start a support group by contacting existing support groups and asking them how they started their organization. It is also recommended that you contact a professional, like a genetic counselor, who can provide guidance.

In addition to donating to your local cancer center, you can donate to research funds such as Lynch Syndrome International ([link url="” target=”_blank”>www.lynchscancers.com), I Have Lynch Syndrome ([link url="” target=”_blank”>www.ihavelynchsyndrome.com), Lynch Syndrome Australia ([link url="” target=”_blank”>www.lynchsyndrome.org.au),and Fight Colorectal Cancer ([link url="” target=”_blank”>http://fightcolorectalcancer.org).

Testing for Muir-Torre syndrome is done by performing a test of someone’s genetic material or DNA. This testing is usually done on a blood or saliva sample. Testing typically focuses on the MLH1 and MSH2 genes and is done by checking the two genes to see if there are any small or large changes in the genes that might cause the disease. If no one in family has previously been tested for changes in these genes, a comprehensive evaluation of both genes is recommended. If a family member has been identified as carrying a specific disease-causing change, the lab will often just test for that specific change. The tests are usually ordered by a genetics health provider after genetic counseling. A genetic counselor will examine an individual’s personal and family history to determine if genetic testing for the MLH1 and/or MSH2 genes is the correct test to order and will provide education before a patient consents to a test to make sure that they have all of the information that they need to make an informed decision about testing. A genetic counselor focused on cancer in your area can be found through the National Society of Genetic Counselors (NSGC) at [link url="” target=”_blank”>www.findageneticcounselor.org.

ClinicalTrials.gov [link url="” target=”_blank”>www.clinicaltrials.gov gives a list of clinical trials currently underway for Muir-Torre or Lynch syndrome. Clinical trials are also listed at Center Watch Patient Notification Service, the National Cancer Institute Search, and through the National Institutes of Health Service.

You may also find research or scientific articles at [link url="” target=”_blank”>www.scholar.google.com by searching "Muir-Torre syndrome".

There are several cancer centers that work with individuals with Lynch/Muir-Torre syndrome, including: Mayo Clinic, The Ohio State University Aultman Cancer Center, Cleveland Clinic Center for Hereditary Colorectal Neoplasia and the Genetic Medicine Clinic at UWMC. Generally, cancer centers that specialize in treating hereditary cancer syndromes will have expertise in this area.

Muir-Torre syndrome results in a predisposition, or higher chance, to develop digestive and uterine cancers, as well as various skin tumors. There is also a predisposition for developing other cancers including: ovarian, small intestinal, stomach, biliary tract, and brain cancer. However, not everyone with Muir-Torre will develop the same type of cancer and some may not develop cancer at all.

Either blood or saliva can be provided for testing, depending on the lab that will be used for testing. A biopsy of a tumor should not be used for genetic testing to identify the variant that may cause Muir-Torre. However, testing a biopsy of a colon cancer for microsatellite instability may be appropriate.

The treatment for Muir-Torre-related cancers depends on the type of cancer and is determined on a case by case basis. However, there are ways to screen for colon, uterine, ovarian, and stomach cancer with the goal of discover cancer at an earlier and more treatable stage. Additionally some cancers related to Muir-Torre can be prevented.
Muir-Torre cancer screening and prevention recommendations include:

This condition is sometimes known as Lynch syndrome II. Lynch syndrome is also known as hereditary non-polyposis colorectal cancer (HNPCC).

Other hereditary cancer syndromes that may have similar symptoms to Muir-Torre syndrome include:

Support groups for Muir-Torre syndrome include:

Muir-Torre syndrome is defined as a genetic, or hereditary cancer. Many people will have disease-causing changes in the MLH1 or MSH2 genes, but in some cases the specific genetic cause can not be defined. However, there are forms of skin tumors and cancers that are not genetic or that can have other genetic causes.

Muir-Torre is a variant of a cancer syndrome called Lynch syndrome. Muir-Torre syndrome is caused by genetic changes, or mutations in the MSH2 or MLH1 genes and everyone who has Muir-Torre syndrome has an increased chance of developing specific types of cancer. The age when those cancers develops is typically earlier than what is typically seen in the general population. Some people will develop cancer as early as in their 30s, others will develop multiple cancers at different ages, some will develop cancers in their 70s or later and some will never develop cancer. Even people in the same family with the same genetic change may develop different cancers at different times.

As of June 2016, there are no clinical trials specific for ‘Muir-Torre’. However, there are multiple studies for individuals with Lynch syndrome and Muir-Torre is considered to be a subtype of Lynch syndrome. The clinical trials that are open or opening range include trials around screening, prevention and treatment. Clinical trial information is available at [link url="” target=”_blank”>www.clinicaltrials.gov.

The skin findings, sebaceous neoplasms or adenomas and the keratocanthomas, are uncommon in the general population. Colon cancers in individuals with Muir-Torre syndrome tend to have a specific genetic signature called microsatellite instability high (MSI-H).