PTEN Hamartoma Tumour Syndrome

PTEN hamartoma tumour syndrome (PHTS)

Last update: July 2026

What is PTEN hamartoma tumour syndrome?

PTEN hamartoma tumour syndrome (PHTS, ORPHA:306498, OMIM:158350, MONDO:0017623) is a rare genetic condition that predisposes to benign growths of some body tissues and to certain cancers and may be associated with neurodevelopmental disorders.

It affects approximately 1 in 9,000 to 1 in 15,000 people. The diagnosis can only be made by testing DNA from blood or equivalent.

People with PHTS have an elevated lifetime risk of developing benign hamartomas and the following cancers (risks by age 70 years according to Hendricks et al. 2023):

Breast cancer: 60-80%
Thyroid cancer: 17-29%
Endometrial (womb) cancer: 6-33%
Kidney cancer: 3-9%
Colorectal (bowel) cancer: 5-15%
•Skin melanoma: 6-12%

Other common features include macrocephaly (larger than average head size) skin nodules, blood vessel anomalies and, in some children, developmental delay or autism spectrum disorders, which may be how PHTS is first identified. A rare non-cancerous brain tumour called Lhermitte-Duclos disease can occur in a small number of adults with PHTS.

What causes PHTS?

PHTS is caused by change in a gene called PTEN. This gene normally acts as a “tumour suppressor”, helping to control cell growth and prevent tumours. In PHTS, one of the two copies of the gene has a pathogenic variant, meaning that it does not work properly, which increases the risk of growths and cancers.

Older names for PHTS, such as Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Lhermitte-Duclos disease, Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome and Proteus-like syndrome are now considered outdated and should no longer be used.

How is PHTS Inherited?

PHTS follows an autosomal dominant pattern. This means that each child of a person with PHTS has a 50% chance of inheriting the PTEN pathogenic gene variant and developing the condition. PTEN pathogenic variants can also arise spontaneously in a child, even if neither parent has PHTS (this is called de novo).

What are the surveillance options in the EU?

According to the ERN GENTURIS cancer surveillance guideline for individuals with PTEN hamartoma tumour syndrome (PHTS) written by ERN GENTURIS:

	*Surveillance*	*Interval*	*From age*	Strength^*
Breast cancer	MRI	as for national high-risk guidelines ^**	25	Strong
	Mammography	as for national high-risk guidelines ^**	40	Strong
	Risk reducing surgery offered	Yes	25	Strong
Thyroid cancer	Ultrasound (US)	Yearly, frequency decreases to every 2-3 years after 2 USs with no suspicious findings	10-18	Surveillance: strong, Age: weak, Interval: moderate
Endometrial (uterus) cancer	Ultrasound (endometrial biopsy can be considered)	Yearly	35-40	Moderate
Renal (kidney) cancer	Baseline imaging	No further surveillance unless required by baseline outcome	35-40	Moderate
Colorectal cancer (bowel)	Baseline colonoscopy preferably in expert centre	No further surveillance unless required by baseline outcome or colorectal cancer family history	35-40	Strong
Skin melanoma	Baseline skin examination by dermatologist or expert	No further surveillance unless required by baseline outcome	30	Moderate

* This grading is based on published articles and expert consensus, strong – expert consensus AND consistent evidence, moderate – expert consensus WITH inconsistent evidence AND/OR new evidence likely to support the recommendation, weak – expert majority decision WITHOUT consistent evidence.

** For instance, BRCA1 guidelines. Most national guidelines for BRCA1 surveillance recommend yearly surveillance with MRI and mammography every 1-2 years.