Cowden syndrome, or PTEN hamartoma tumour syndrome, is a hereditary cancer syndrome.

PTEN hamartoma tumour syndrome

PTEN hamartoma tumour syndrome (PHTS) is a hereditary condition caused by a faulty (disease-causing) PTEN gene.

‘Hamartoma’ is a general term for a benign, or non-cancerous, tumour-like growth. PHTS is a broader term which includes Cowden syndrome (CS).

PTEN is a gene that makes an important protein to control cell growth and division. When a fault occurs in the PTEN gene, the protein cannot be made properly and cell growth becomes uncontrollable, which often leads to the development of benign tumours or cancer.

In rare cases, individuals with faults in other genes like AKT1 and PIK3CA can present with features similar to CS. Genetic testing can clarify where the gene fault lies.

What is Cowden syndrome?

CS occurs in an estimated one in 200,000 people. Individuals with CS may develop both benign and malignant (cancerous) tumours in the breasts, uterus, thyroid, gastrointestinal tract, skin, tongue and gums.

People with CS are also at higher risk of developing various cancers.

What is hereditary cancer?

Hereditary cancer makes up about 5-10% of all cases of cancer. Some genes function to protect us from cancer. When they are not working well, it causes hereditary cancer. We refer to genes that are not working well as faulty genes.

Individuals who carry a faulty cancer gene(s) have a higher chance of developing certain cancers over their lifetime compared to the general population. The types of cancers that they may be at increased risk of will depend on the gene(s) involved.

If you have a faulty cancer gene, you may be at increased risk of developing certain cancers. As genes are shared among family, other family members may have inherited the faulty gene and may be at increased risk of cancer too.

Hereditary cancer accounts for up to 10% of all cases of cancer.

What is genetic testing?

Genetic testing is offered to individuals where a hereditary cause of their personal and/or family history of cancer is suspected.

Genes contain the instructions that our body reads to carry out different functions. Genetic testing involves analysing your genes to understand if there are faults (i.e., mutations) that may increase the risk of diseases like cancer.

How is genetic testing done?

• Genetic testing is typically a one-time blood test.
• If a blood sample cannot be taken, other sample sources (e.g., skin or saliva) may be used.

What are the possible results of genetic testing?

There are 3 types of results you may receive:

The common cancers in individuals with a faulty PTEN gene

• Breast Cancer
• Thyroid cancer
• Uterine cancer
• Kidney cancer
• Colon cancer
• Melanoma
  

Note: The cancers associated with a faulty PTEN gene and their risk estimates may change as more information is available.

Other non-cancer features associated with CS include:

• A large head size (macrocephaly)
• Benign tumours of the thyroid, breast and endometrium
• Bumps/growths on the skin (trichilemmomas) or in the mouth (papillomatosis)
• Polyps (growths) in the colon or intestines
• Autism
• Developmental delay
• Blood vessel malformations or haemangiomas (strawberry marks)
• Benign tumours (lipomas) commonly found on the upper back and shoulders
  
  

How is CS inherited?

Cowden syndrome follows a dominant inheritance pattern. This means that having one copy of a faulty PTEN gene will result in the diagnosis of CS and an increased risk of tumours/cancer. It affects both males and females.

Everyone has 2 copies of each gene in their body’s cells:

• 1 copy comes from our father
• 1 copy comes from our mother

A parent with a faulty gene(s) has a 50% chance of passing down their faulty gene(s) to their children. A child, sibling or parent of a family member with a faulty gene(s) has a 50% chance of also inheriting the same faulty gene(s). Extended relatives may also inherit the faulty gene(s).

How is CS diagnosed by doctors?

Individuals can be diagnosed with CS through a physical examination and clinical evaluation by a doctor with experience in managing the condition, to assess if the clinical diagnostic criteria of CS is met.

If a patient is found to meet clinical testing criteria or to have features suggestive of CS, genetic testing may be offered.

Who should undergo testing for CS?

Genetic testing is usually recommended for individuals who meet one or more of the criteria below:

• Clinically diagnosed with CS
• A family member who has a clinical diagnosis of CS/PHTS for whom testing has not been performed AND meets:
  • Any two major criteria; OR
  • One major and two minor criteria; OR
  • Three minor criteria
• A previously identified faulty PTEN gene in the family
  

Note: The criteria outlined here may change as more information is available.

How can your genetic test result help you?

1. Personalised management
   

   Your genetic test result may help confirm a clinical diagnosis of CS. Understanding if you have CS provides you with options for managing your risk of tumours/cancer.
   
   For example, screening options may be recommended to you which can help to detect tumours/cancer at its earliest, most treatable and manageable stage.
   
   In some cases, you may choose to undergo surgery that can help to reduce your risk of developing cancer (not standard management). For individuals planning a family, dedicated reproductive options may also be available.

2. Familial implications
   

   Your genetic test result can also help you understand if other family members are at risk of CS. They can subsequently consider their own testing (predictive testing) to clarify their carrier status to determine tumour and cancer risks.
   
   Family members who have inherited the same faulty gene may be at increased risk of tumours and cancer and can benefit from management options such as screening (to detect tumours and cancer at an early and manageable stage) or surgery (to reduce their risk of cancer).
   
   Family members who did not inherit the faulty gene can avoid unnecessary screening and worry. Their children will also not be at risk.

What can I do to manage my increased risk of cancer?

Screening

Screening helps to detect (and in some cases treat) tumours and/or cancer at an early and manageable stage.

• General
  • Physical examination by a doctor with experience in managing CS
• Breast cancer (for females)
  • Practice breast self-awareness
  • Regular clinical breast examination
  • Breast mammograms and/or magnetic resonance imaging (MRI) scans
• Uterine (endometrial) cancer (for females)
  • Prompt reporting of symptoms (e.g., abnormal uterine bleeding)
  • Consider endometrial biopsies (limited evidence of benefit)
• Kidney cancer
  • Consider kidney ultrasounds
• Skin cancer
  • Examinations by a skin doctor (dermatologist)
• Colorectal cancer
  • Colonoscopies
• Thyroid cancer
  • Thyroid ultrasounds

Your managing doctor(s) will discuss screening recommendations with you in greater detail, which may be tailored based on your personal and medical history. The age and onset for screening may depend on your personal and/or family history of cancer. Screening guidelines may change as more information is known.

Risk-reducing surgery

In some cases, risk-reducing surgery may be offered to help reduce the risk of cancer.

• Breast cancer (for females)
  • Consider risk-reducing surgery to remove breast tissue (bilateral mastectomy)
• Uterine (endometrial) cancer (for females)
  • Consider risk-reducing surgery (hysterectomy) to remove the womb (uterus) in certain cases, upon family completion

Your managing doctor(s) will discuss these options with you in greater detail. These surgeries reduce cancer risk significantly but do not remove the risk entirely.