PTEN Hamartoma Tumour Syndrome

PTEN Hamartoma Tumour Syndrome (PHTS)

What is PTEN Hamartoma Tumour Syndrome?

PTEN Hamartoma Tumour Syndrome (PHTS, ORPHA:306498) is a rare genetic condition that causes an increased risk for certain cancers, benign growths, and neurodevelopmental conditions. Its prevalence is estimated as 1 in 200,000 - 250,000, although the condition may be underdiagnosed. For a person with PHTS, three different studies have found an increased lifetime risk for certain types of cancer. The study with the largest number of patients found the following cancer risks (up to the age 70 of years): breast (67-85%), thyroid (6-38%), kidney (2-34%), uterus (19-28%), colorectal (9-20%) and melanoma (0-6%).

A benign tumour of the cerebellum called Lhermitte-Duclos disease can occur in a small minority of adults with PHTS. Macrocephaly (larger than average head size) is common and some children with PHTS are first identified because they have developmental delay and autism spectrum disorders.

What causes PHTS?

PHTS is caused by a pathogenic germline variant of the PTEN gene. Previously some people may have been diagnosed with Cowden's syndrome or Bannayan-Riley-Ruvalcaba syndrome, which were based on their personal medical history and the characteristics they have developed.

One of the roles of the PTEN gene is to act as a tumour suppressor gene, which means that when it works properly, PTEN helps suppress the growth of all cells that are trying to grow out of control and become tumours.

How is PHTS Inherited?

Each child of an affected person has a 50% chance of inheriting their PTEN gene mutation and thus also develop PHTS. It is also possible for PTEN mutations to spontaneously occur in a next generation.

What are the surveillance options in the EU?

According to the Cancer surveillance guideline for individuals with PTEN Hamartoma Tumour Syndrome (PHTS) written by ERN GENTURIS:

  • Breast (women): start high-risk breast surveillance with yearly MRI from age 30 and additional yearly mammography from age 40
  • Thyroid: annual ultrasound starting at age 18
  • Kidney: ultrasound every two years starting at age 40
  • Uterine: not recommended, in individual cases one can start with yearly ultrasound starting at age 40
  • Colon: follow-up dependent on number and type of polyps, no standard recommendations for surveillance
  • Skin: not recommended


More information regarding PTEN hamartoma tumour syndrome can be found on:

GeneReviews® - PTEN hamartoma tumour syndrome
Orphanet: PTEN hamartoma tumor syndrome

Clinical practice guideline


PHTS guideline - Cancer surveillance guideline for individuals with PTEN Hamartoma Tumour Syndrome (PHTS)


ERN GENTURIS care pathway

Care pathway - PTEN Hamartoma Tumour Syndrome (PHTS)


ERN GENTURIS patient journey

Patient journey - PTEN hamartoma tumour syndrome (PHTS)


ERN GENTURIS publications

Thematic Group 4: Other rare – predominantly malignant – genturis

PTEN hamartoma tumour syndrome (PHTS)


ERN GENTURIS healthcare providers

A list of healthcare providers with expertise in Thematic Group 4: Other rare - predominantly malignant - genturis can be found here.


Patient associations for hereditary cancer syndromes

A non-exhaustive list of patient associations for genetic tumour risk syndromes in EU member states can be found here.