What Is Muir Torre Syndrome?

Overview

Definition of Muir-Torre Syndrome (MTS) 

Muir-Torre syndrome (MTS) is a rare genetic disorder that increases your chances of developing certain types of cancers. This is an autosomal dominant disorder caused by a defect in your genes and is a variant of Lynch syndrome. It is commonly associated with colorectal cancer. The tumours can be benign (non-cancerous) or cancerous, developing on the skin or the gastrointestinal tract.¹

Brief history and discovery

The term “Muir-Torre syndrome” was named after Muir who discovered it in 1967 and Toree, a year later in 1968 after presenting his findings at a meeting.¹

Importance of understanding MTS

Patients who are diagnosed with MTS have a higher chance of developing many types of cancer, including ovarian, colorectal, endometrial, and small bowel cancers. Early detection and effective treatment can increase the chances of a better outcome.¹

In this article, we will explain in depth, the symptoms, diagnosis and treatments of Muir-Torre Syndrome.

Understanding Muir-Torre Syndrome 

Overview of MTS 

Our DNA is a double helix strand made up of four bases: Adenine (A), Guanine (G), Cytosine (C), and Thymine (T). These bases pair up with each other, A and T, G and C. These bases can be mismatched through replication errors caused by DNA damage. A DNA repair pathway called DNA mismatch repair will correct these mistakes. This process is vital to maintain genomic stability, which refers to the ability to maintain the structure and sequence of the genome.²

However, if the damage is too severe and surpasses the repair capacity, it can result in mutations in the mismatch repair genes, increasing the likelihood of mismatched bases and resulting in disorders like Muir-Torre Syndrome. Muir-Torre syndrome is an autosomal dominant disorder, affecting one of your non-sex chromosomes, referred to as autosomes.¹

Associated genetic mutations  

MSH2, MLH1, MSH6 and PMS2 are the genes associated with Muir-Torre syndrome. The majority of genetic mutations occur in the MSH2 gene.³

Connection to Lynch Syndrome

Muir-Torre syndrome is described as a variant of hereditary non-polyposis colorectal cancer (HNPCC), which is also known as Lynch syndrome. 

Not all cases of Muir-Torre syndrome are variants of Lynch syndrome. They can also be associated with another syndrome called MUTYH-associated polyposis (MAP). 

Clinical Manifestations 

Skin manifestations

Skin manifestations are common in patients with Muir-Torre syndrome. They can be either sebaceous adenomas or sebaceous carcinomas on the skin.⁴

Sebaceous adenomas

These appear as a small harmless bump on the skin, commonly found on the head and neck. Adenoma is a term used to describe non-cancerous tumours. They are not cancerous and usually do not require any treatments. If they are bothersome, you can speak to your doctor to discuss removing the bump through surgery. They typically do not recur after recovery.⁵

Sebaceous carcinomas 

Sebaceous carcinoma is a progressive malignant skin cancer. It begins in the sebaceous glands, where the natural oils are produced. As we have sebaceous glands all over the body, this type of cancer can begin anywhere but most commonly affects the upper eyelid. You may notice a firm yellow bump or red crusty skin near your eyelashes.

It may not be sebaceous carcinoma, sebaceous carcinomas are extremely rare with 1% of eyelid tumours being sebaceous carcinomas.³ These symptoms may resemble non-cancerous conditions like pink eye, chalazion, blepharitis and styes. You must speak to your GP if you see unusual growth on your eyelids. 

Internal malignancies associated with MTS

Colorectal cancer is the most common cancer associated with MTS. Other cancers such as gastrointestinal tract tumours, genitourinary cancers, breast, lung, and haematological (blood) account for ¼ of MTS cases.³

Diagnosis of Muir-Torre Syndrome 

Clinical criteria for diagnosis

Sebaceous tumours are common in MTS which can guide clinicians to evaluate the diagnosis of MTS. To obtain a diagnosis of MTS, the clinical criteria must include at least one sebaceous tumour and cancerous cells found in the gastrointestinal or genitourinary tract, that have not been caused by receiving treatments like radiotherapy. 

Screening recommendations for patients and families

It is expected that the patient will receive a thorough physical examination including a family history of MTS. The most common area affected is the face, specifically on the nose and eyelids. You may be recommended other screening tools to confirm the diagnosis like urinalysis or routine screening tools like a colonoscopy or rectal ultrasonography.⁷

Genetic testing and molecular analysis

You may be recommended genetic testing for genetic mutations associated with MTS. A sample of your blood will be taken for laboratory analysis. This may take weeks for a complete analysis. 

Management and Treatment 

Multidisciplinary approach to managing MTS 

A multidisciplinary approach involves collaboration among various medical specialists. A dermatologist handles skin assessments and treatments, genetic counsellors provide insights into your genetic information. Additionally, oncologists manage internal cancer that may develop. 

Surveillance and screening protocols 

If the diagnosis confirms MTS, the patient should be monitored regularly for suspected tumours growing internally and on the skin. A colonoscopy will be recommended and you can begin getting screened as early as 18 years old. This is routinely performed every 1-2 years. Furthermore, an upper and lower gastrointestinal endoscopy is common for monitoring patients with MTS.¹

Surgical and non-surgical interventions 

A large number of sebaceous growths may be challenging because they can cause disfigurement, making treatment more complex. You may be offered local excision or cryotherapy to remove the non-cancerous growths if you’re experiencing discomfort or low self-esteem.¹ Having a conversation with your doctor can help you make the appropriate decision.

Psychological and familial support

Being diagnosed with MTS can cause feelings of uncertainty, anxiety or depression. If you’re feeling overwhelmed, speak to someone you trust like your doctor or your family. They can provide support as much as possible.

Prognosis and Outcomes 

Variability in disease expression and prognosis 

Muir Torre syndrome can vary significantly from person to person. Some may have fewer symptoms or skin growths while others may experience severe manifestations or be at a higher risk of certain cancers. Determining the prognosis can differ, emphasising the importance of personalised treatment and close monitoring for each individual.

Impact on quality of life 

You may find that being diagnosed with MTS can have an impact on your quality of life. Several factors including multiple skin growths, potential disfigurement, and risk of developing internal cancers can lead to physical discomfort and emotional distress. Needing frequent monitoring and possible surgeries may cause anxiety. Seeking support from healthcare professionals can be vital in helping you navigate the challenges and maintain your quality of life.

Importance of early detection and management

Regular screening, genetic testing and a collaborative effect among healthcare specialists are key to early detection, treatment and ongoing management of MTS. Men should attend their annual testicular and prostate exams and women should attend their breast and cervical screening.

Research and Future Directions 

Researchers are continuously finding ways to advance our understanding of Muir-Torre syndrome, exploring specific genes and mutations involved. Additionally, they are finding ways to improve screening and diagnostic methods to detect the condition earlier or rule it out from other conditions with similar symptoms.⁸ Raising awareness for Muir Torre syndrome is the driving force to accelerate research in this area, and personalising treatments that benefit the lives of patients. 

Summary

Muir-Torre syndrome is a rare disorder that increases the chances of developing certain types of cancers including skin cancer, gastrointestinal and colorectal cancer. With an individual who may be at a high risk of developing cancer, it’s important to be directed to the appropriate care and attend screening appointments with a healthcare specialist to detect possible signs of cancer. Being diagnosed with Muir-Torre syndrome can hurt your mental well-being. Seek guidance from people you trust or a medical professional as they can help you navigate the challenges of your condition.