Conditions > PTEN hamartoma tumour syndrome (PHTS)

PTEN hamartoma tumour syndrome (PHTS)

Clinical picture

PTEN hamartoma tumour syndrome (PHTS) refers to a spectrum of conditions that are characterised by multiple hamartomas. These conditions include:

Cowden syndrome: associated with a high risk for benign and malignant (cancerous) tumours of the thyroid, breast and uterus. Affected people may also have macrocephaly and characteristic skin abnormalities
Bannayan-Riley-Ruvalcaba syndrome: characterised by macrocephaly (large head size), hamartomas of the intestines (called hamartomatous intestinal polyps) and dark freckles on the penis
Proteus syndrome: characterised by overgrowth of the bones, skin and other tissues
Proteus-like syndrome: people with many of the signs and symptoms associated with Proteus syndrome, but who do not meet the diagnostic criteria

PTEN hamartoma tumour syndrome is caused by changes (mutations) in the PTEN gene and is inherited in an autosomal dominant manner. Treatment is based on the signs and symptoms present in each person.

Symptoms

Symptoms of people with PHTS can vary enormously. Some patients present a large range of complaints; others barely show any symptoms at all. Among the most common symptoms are:

Skin abnormalities:
- small lumps on hands, feet, arms or legs
- small lumps around the nose, known as facial trichilemmomas
- subcutaneous lipomas
Abnormalities in mucous areas:
- small lumps on lips, tongue and in the mouth
- grooves and lesions of the tongue
Macrocephaly:
- children with PHTS often have a relatively larger head than other children
Benign tumours:
- benign tumours can occur anywhere in the body but are typically found in the thyroids, breasts and the intestinal tract
Raised chance of cancer:
- benign tumours can always turn malignant, and this occurs mostly in the thyroid and the breasts. Other cancers associated with PHTS are endometrial cancer, bowel cancer, kidney cancer and skin cancer
Lhermitte-Duclos Disease
- This disease causes benign tumours to develop in the cerebellum. These can lead to balance and sight problems, but also headache and nausea
Learning difficulties

Cause

PHTS is caused by a germline mutation of PTEN, a tumour suppressor gene. PTEN stands for phosphatase tensin homologue. A tumour suppressor is a gene that slows down cell division, repairs damage to cell DNA and tells cells when to die, in a normal process called apoptosis. Mutations in a tumour suppressor gene often lead to cancer. The PTEN gene regulates the production of an enzyme (protein tyrosine phosphatase) that is believed to be important in stopping cell growth and starting apoptosis. Researchers believe that the PTEN gene plays a broad role in the development of human malignancies.

PHTS is inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the abnormal gene on from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.

Diagnosis

Given the rarity of PHTS and the wide array of symptoms, it is not very likely that a GP will immediately suspect PHTS. A set of major and minor criteria serves to determine whether someone has PHTS or not. Someone has PHTS when:

three major criteria are met, one of which being macrocephaly, Lhermitte-Duclos disease or hamartoma in the digestive tract;
two major and three minor criteria are met.

Major criteria:

breast cancer
thyroid cancer
endometrial cancer
hamartomas in the digestive tract
macrocephaly
Lhermitte-Duclos disease
flecking of the glans of the penis
lumps inside the oral cavity and skin abnormalities

Minor criteria:

an affliction in the autism spectrum
intestinal cancer
abnormalities in the oesophagus
three or more lipomas
arrested development
kidney cancer
fatty lumps on the testes
enlarged thyroids
certain vascular disorders
several benign breast tumours

Additional DNA research can confirm the diagnosis.

Treatment

PHTS is a genetic disease and therefore incurable. Patients who have been diagnosed with the disease are advised to undergo regular check-ups. Patients under the age of 18 will be examined annually and have their thyroids checked by ultrasound. From the age of 40, the colon gets examined as well once every five years. Women between 25 and 75 undergo annual breast exams and from the age of 30 also gynaecological tests.