What is PTEN hamartoma tumor syndrome?
PTEN hamartoma tumor syndrome (PHTS) is a term for 4 related syndromes that are caused by a mutation in the PTEN gene. The term “syndrome” refers to a group of features that often occur together. The syndromes grouped under PHTS are:
- Cowden syndrome (CS)
- Bannayan-Riley-Ruvalcaba syndrome (BRRS)
- PTEN-related Proteus syndrome (PS)
- Proteus-like syndrome
A hamartoma is an overgrowth or abnormal growth of cells and is similar to a benign (noncancerous) tumor. It is a common feature in all 4 syndromes grouped under PHTS.
People with CS often have macrocephaly (a large head size), bumps in the mouth, and certain skin conditions on the face, hands, and feet. People with CS also have an increased risk of developing tumors (both benign and cancerous) of the thyroid, breast, and uterus. In some rare cases, people with CS may have polyps (growths) in the intestines, cancer of the kidneys, skin, or brain, and developmental delays. The symptoms of CS usually appear when people are in their late 20s.
The other 3 syndromes grouped under PHTS are less well defined. The symptoms of BRRS are present at birth. People with BRRS also have macrocephaly, as well as polyps in the intestines, benign tumors of fatty tissue called lipomas, and colored spots on the tip of the penis.
PTEN-related PS is another syndrome in which symptoms are present at birth. The symptoms can vary widely and may include hamartomas of any part of the body. Proteus-like syndrome is very similar to PTEN-related PS, but the symptoms are not as severe.Back to top
How common is PHTS?
PHTS is thought to be underreported, and many people who have it may not be diagnosed in their lifetime. About 250,000 people in the world have been diagnosed with PHTS to date. CS is the most common sub-syndrome of PHTS, occurring in about 1 in every 200,000 people. PTEN-related Proteus syndrome is rare; only about 120 cases have been reported.
PHTS can be detected through genetic testing.Back to top
What does a negative PTEN test result mean?
A negative result means that no PTEN gene mutation was found. This can happen if:
- You have a mutation in the PTEN gene that is not detectable by the testing method used.
- You may have a mutation in a different gene. For example, even if you tested negative for a PTEN mutation, your genetic counselor may recommend testing for mutations in a different gene that could help explain your personal and/or family history.
- Your personal or family history of cancer could have happened by chance. Uterine cancer, in particular, is a common cancer. It may occur in several people in a family without being caused by a hereditary genetic mutation.
- There is a genetic mutation in your family, but you did not inherit it.
What does a “variant of uncertain significance” (or “ambiguous”) test result mean?
Genes are written in chemical “letters” called bases. We call the wrong spelling of a gene a “mutation,” and a mutation can cause an increased risk of cancer. However, some spelling changes in genes do not cause disease. We are still learning which spellings are normal (harmless) and which may cause disease. These kinds of uncertain changes are called “variants of uncertain significance.”
If you have a variant of uncertain significance in your PTEN gene, we may not be able to tell you whether or not you are at increased risk for cancer. We will make cancer screening recommendations for you based on your family history. We may suggest testing certain relatives to learn more about the variant, but this information will probably not be helpful in predicting cancer risks for your relatives. Future research may make it clearer whether a variant of uncertain significance leads to increased risks of cancer.Back to top
What does a positive PTEN test result mean?
A positive PTEN test result means that a mutation in the PTEN gene was found. People with a PTEN mutation are at an increased risk for developing the different symptoms and tumors seen in one of the PHTS syndromes. These risks vary based on the different syndromes and may vary between people with the same syndrome.Back to top
How should people with a PTEN mutation manage their cancer risks?
Most of the cancers that develop in people with a PTEN mutation are highly treatable when detected early. The primary goal of screening is to detect cancers early. Men and women with PTEN mutations should follow cancer screening recommendations from their doctor. These screenings are described below.
This screening should be started at age 18. Thyroid ultrasound, which uses sound waves to create images, is the best method. It should be done once a year.
- Both men and women should be aware of how their breasts normally look and feel.
- Women should have:
- A mammogram every year beginning at age 25. Researchers are looking for ways of improving mammograms, like contrast-enhanced screening mammography.
- Magnetic resonance imaging (MRI) of the breast every year beginning at age 25.
- Breast exams by a doctor or nurse every 6 months.
- Ultrasound of the breast (in certain situations).
Women should have endometrial biopsies every 1 to 2 years starting between 30 to 35 years of age. If you have any changes in your menstruation (period), you should be tested more often.
Men and women should be screened for colon cancer by age 35. Colonoscopy is the best method. Screening should be done every 5 to 10 years. If you have any risk factors, speak with your doctor about how often you should have a colonoscopy.
Men and women should have yearly skin exams by a dermatologist. The skin changes seen in PHTS are usually cosmetic and not life-threatening. You may need to use certain skin creams and have minor skin surgery, as recommended by your dermatologist.
Men and women should have an ultrasound of the kidneys every 1 to 2 years starting at age 40.
Surgery is an alternative approach to screening. Women with a PTEN mutation may choose to undergo surgery to try to prevent certain cancers. Because breast and uterine cancers are common among women with PTEN mutations, they may choose to have their breasts or uterus removed. Surgery to remove both breasts (risk-reducing bilateral mastectomy) and surgery to remove the uterus (hysterectomy) are options.Back to top
If I have a PTEN mutation, what are the risks to my children?
If you have a PTEN mutation, each of your children (or future children) has a 50% chance of inheriting that mutation. It is important to remember that just inheriting the mutation does not always mean that a person will definitely develop cancer.
Some people with mutations want to know when their children should be tested. Since children are not at high risk for tumors, it is recommended that children wait to be tested until they reach adulthood and can then choose when they wish to learn their status. Many choose to be tested around the age when screening would begin should they test positive.Back to top
If I have a PTEN mutation, what are my options for having children?
If you have a PTEN mutation, you may want to learn about options for family planning (starting a family or having more children). For example, embryos can be tested for the family’s genetic mutation before they are even implanted in a woman’s uterus. This process is called preimplantation genetic diagnosis (PGD). PGD is performed in combination with in vitro fertilization (IVF), and may be an option for families who wish to have children without the hereditary cancer risk. To learn more, ask for a referral to a PGD-IVF specialist before attempting pregnancy.
Other possible family planning options include having children with the assistance of donor eggs or sperm or through adoption.Back to top
What if I have questions?
If you have any questions or concerns, please contact the MSK Clinical Genetics Service at 646-888-4050.Back to top