Muir Torre Syndrome

What is Muir-Torre syndrome?

Muir-Torre syndrome is a rare genetic disorder that raises your lifetime risk of developing several types of cancer. Muir-Torre syndrome is characterized by cancerous or noncancerous skin tumors that develop in combination with one or more internal cancerous tumors, often in your gastrointestinal tract.

Is Muir-Torre syndrome the same as Lynch syndrome?

Muir-Torre syndrome is in most cases a variant of Lynch syndrome. Lynch syndrome refers to a group of related genetic mutations that can increase your risk of developing cancer. Healthcare providers may also use the term hereditary non-polyposis colorectal cancer (HNPCC) to describe the same condition.

However, up to a third of Muir-Torre syndrome cases may be related to a different hereditary cancer syndrome called MUTYH-associated polyposis syndrome. Healthcare providers now define MTS related to Lynch syndrome as type 1, and MTS related to MUTYH-associated polyposis syndrome as type 2.

How common is Muir-Torre syndrome?

Only around 200 cases of Muir-Torre syndrome have been recorded, mostly from white populations in developed Western nations. It occurs in about 9.2% of people with HNPCC. It appears to be slightly more common in men and people assigned male at birth (AMAB) than in women and people assigned female at birth (AFAB), by a ratio of 3:2.

What are the symptoms of Muir-Torre syndrome?

Symptoms include skin lesions and other symptoms related to the specific cancerous tumors you might have. Skin lesions may develop before, with or after you develop cancerous tumors. Regardless, skin lesions are often the first symptoms you’ll notice. Other cancers may not cause symptoms right away.

What does Muir-Torre syndrome look like?

Skin lesions in Muir-Torre syndrome may include:

• Sebaceous adenomas. These are the most common skin lesions associated with Muir-Torre syndrome, occurring in 80% to 99% of cases. Sebaceous adenomas are benign (noncancerous) tumors that occur in your sebaceous glands, the oil-secreting glands found in hair follicles. Sebaceous adenomas typically occur on your head or neck, but in Muir-Torre syndrome they often occur on your trunk (chest, abdomen, pelvis or back). They look like small, firm, yellowish or skin-colored bumps.
• Sebaceous carcinoma. Muir-Torre may also present with a cancerous form of the sebaceous gland tumor. This skin cancer looks like a sebaceous adenoma, but it spreads rapidly and often occurs on eyelids. A sebaceous carcinoma may bleed or secrete a crusty discharge.
• Keratoacanthoma. This is a different type of skin tumor that also occurs in hair follicles on your head, neck, trunk or arms. It can be cancerous or benign. It appears as a small, dome-shaped bump with visible blood vessels and a knobby keratin core. It grows quickly, within weeks, up to 3 centimeters wide, then slowly diminishes over several months or years. You may have one or many.
• Fordyce spots. Since most tumors in MTS involve your sebaceous glands, some healthcare providers look for ectopic sebaceous glands, also known as Fordyce spots, as a symptom. These are enlarged and slightly raised sebaceous glands that appear in hairless areas on your skin, often around your mouth. Studies suggest they may occur more frequently with MTS.

What cancers are linked to Muir-Torre syndrome?

The most common cancers and their symptoms include:

• Colorectal cancer. This is the most common cancer associated with Muir-Torre syndrome, occurring in around half of cases. It develops in the lining of your colon or rectum (your large intestine). Colorectal cancer in Muir-Torre syndrome may develop 15 to 20 years earlier than it usually does, with the average age of onset around 50. It may also advance more quickly. Symptoms include stomach pain and bloating, poop changes and rectal bleeding.
• Stomach cancer is another common cancer in Muir-Torre syndrome. It can also cause stomach pain, bloating and blood in your poop, as well as indigestion, nausea and loss of appetite.
• Urinary cancer. Urothelial carcinoma, also called transitional carcinoma, affects your urothelium, the tissue that lines your urinary system. It can cause pain or bleeding in your pee.
• Endometrial cancer. This cancer affects the endometrium, the lining of your uterus. It may cause lower abdominal pain or pelvic pain and vaginal discharge or vaginal bleeding.

Other cancers that may occur include:

• Ovarian cancer.
• Prostate cancer.
• Bladder cancer.
• Kidney cancer.
• Penile cancer.
• Testicular cancer.
• Breast cancer.
• Small intestine cancer.
• Liver cancer.
• Bile duct cancer.
• Pancreatic cancer.
• Adrenal cancer.
• Lung cancer.
• Blood cancer.
• Brain cancer.
• Laryngeal cancer.
• Salivary gland cancer.
• Bone cartilage cancer.

What causes Muir-Torre syndrome?

Muir-Torre syndrome results from a mutation in one of your genes. Genetic mutations are changes to your DNA sequence that happen during cell division when your cells make copies of themselves. When an abnormal cell replicates itself in your body, it can lead to various disorders, including cancer.

Which gene mutations cause it?

Type 1 Muir-Torre syndrome is caused by a mutation in one of your mismatch repair genes, the genes responsible for fixing errors in your DNA sequence. When these genes can’t repair errors, abnormal cells build up in your tissues. Most (90%) of the time, it’s the MSH2 gene, but a few others may be involved, including MLH1, MSH6 and PMS2.

Type 2 MTS is caused by a mutation in the MUTYH gene, a gene responsible for repairing oxidative damage to your DNA. Oxidation causes changes to your DNA molecule that can lead to unregulated cell production (cancer). When the mutated gene can’t repair the damage, the damage replicates.

Is Muir-Torre syndrome hereditary?

Most cases are inherited, though occasionally an original genetic mutation occurs without family precedent. Up to 60% of cases can be traced to a family history of Muir-Torre syndrome. But since not everyone with the gene mutation is diagnosed with MTS, this family pattern isn’t always known.

Sometimes people have latent MTS without any symptoms or knowledge of the disease. And sometimes, latent MTS becomes active when your immune system is suppressed. This has occurred in some people who received solid organ transplants and began taking immunosuppressant medications.

How do you inherit Muir-Torre syndrome?

Type 1 MTS is an autosomal dominant condition. That means you only need one copy of the mutated gene to inherit the condition. If you have one parent with the genetic mutation, you have a 50% chance of inheriting it. But how it manifests for you may be different from the parent you inherited it from.

Type 2 MTS is an autosomal recessive condition. That means both of your parents have to have the same gene mutation for you to inherit it. This is much less common. However, parents carrying only one copy of the autosomal recessive gene won’t have any symptoms themselves, so they may not know.

How is Muir-Torre syndrome diagnosed?

Your healthcare provider might suspect Muir-Torre syndrome if you have the characteristic skin tumors, especially if they’re mostly on your trunk or if you’ve developed them relatively young. They might ask if you have any other symptoms that could indicate internal cancer, or if you have a family history of cancer.

What tests help to diagnose MTS?

Your provider might suggest some initial screening tests for MTS before ultimately recommending genetic testing. For example, they might stain and examine a tissue sample from one of your skin tumors to look for specific gene mutations in the sample. This is called immunohistochemistry (IHC).

Based on these test results and/or other data, your provider might recommend genetic testing for the gene mutations involved in Muir-Torre syndrome. They’ll look at a sample of your blood for mutations in the mismatch repair genes MSH2, MLH1, MSH6 and PMS2, or the base excision repair gene, MUTYH.

What type of cancer screenings should someone with Muir-Torre syndrome have?

Healthcare providers recommend regular cancer screenings for people with Muir-Torre syndrome.

Tests may include:

• Colonoscopy.
• Upper endoscopy or EGD.
• Prostate exam.
• Mammogram.
• Pelvic exam.
• Pap smear.
• Urine cytology.
• Liver function tests.
• Complete blood count (CBC).
• Physical exam.
• Skin exam.
• Chest X-ray.

What is the treatment for Muir-Torre syndrome?

Management of Muir-Torre syndrome focuses on finding and removing cancer when it occurs. You’ll have regular cancer screenings and biopsies of any suspicious tissues. If your provider finds cancer, they’ll treat it according to the type and stage. Surgical removal is usually the first-line treatment.

Other treatments for cancer include:

• Chemotherapy.
• Radiation therapy.
• Hormone therapy.
• Immunotherapy.
• Targeted therapy.
• Bone marrow transplant.

An oral retinoid medication called isotretinoin can help prevent new skin tumors from developing. If your colonoscopy finds many colon polyps, which raise your risk of developing colon cancer, your healthcare provider might recommend a prophylactic colectomy to remove part or all of your colon.

Is there any prevention for Muir-Torre syndrome?

In general, no — you inherit the condition at birth. However, not everyone develops symptoms, and those who do may have milder or more severe diseases than their biological parent had. Scientists don’t know why this is, though they’ve observed that a suppressed immune system can lead to a worse outcome.

Knowing that you carry the gene mutation may lead you to make certain preventive choices. For example, genetic testing and genetic counseling may prevent you from passing the condition on to a biological child. Knowing can also help you catch and treat cancer sooner, preventing worse outcomes.

What is the prognosis with Muir-Torre syndrome?

Your prognosis (outlook) will depend on how many cancers you develop and how far they advance. Statistically, nearly half of people with Muir-Torre syndrome develop more than one cancer. More than half of people develop metastatic cancer, cancer that’s spread from where it started and can be especially difficult to treat.

Cancer in Muir-Torre syndrome appears at the average age of 50. It tends to progress (get worse) more quickly than in the general population, so catching it early is key. It also tends to recur (come back) more often after being removed, so frequent follow-up screenings will be important after you’ve been treated for cancer.

A note from Cleveland Clinic

Muir-Torre syndrome is rare, but that doesn’t make the diagnosis easy to receive. A condition that’s embedded in your very DNA may seem very hard to defeat. But knowledge is power. With timely recognition and treatment, you and your healthcare provider will be armed to meet the challenge.