PTEN Hamartoma Tumor Syndrome (PHTS)

What PTEN does

The PTEN gene makes a protein that acts as a brake on cell growth and division. When one copy of the gene does not work, cells in many tissues can grow more than they should. This leads to hamartomas (benign overgrowths of normal tissue) and a higher chance of cancer.

Conditions within PHTS

These are now viewed as one condition with variable expression.

Signs and symptoms

• macrocephaly: a large head, present in nearly everyone with PHTS
• skin and mouth findings: small skin-colored bumps on the face (trichilemmomas), warty papules on the hands and feet, small bumps on the gums and tongue (papillomatosis), lipomas
• gut polyps: many hamartomatous colorectal polyps and polyps throughout the digestive tract
• thyroid: benign thyroid nodules, goiter, Hashimoto's thyroiditis
• breast: fibrocystic changes and benign tumors
• uterine fibroids
• vascular malformations
• Lhermitte-Duclos disease: a rare benign growth in the cerebellum
• neurodevelopment: autism spectrum disorder or developmental delay in some children

Cancer risks

Lifetime risks are substantially higher than in the general population. Estimates vary between studies:

Breast and thyroid cancers can occur at younger ages than usual.

Diagnosis

• Clinical criteria: combinations of major and minor features, such as breast cancer, macrocephaly, multiple gut hamartomas, skin findings and thyroid cancer
• Genetic testing: a blood or saliva test for PTEN variants confirms the diagnosis. Testing is offered to people meeting criteria, children with macrocephaly plus autism or developmental delay, and relatives of known carriers.
• Genetic counseling before and after testing

Screening and management

Screening recommendations, based on NCCN guidance, typically include:

• Thyroid: ultrasound every year starting at diagnosis, including in childhood
• Breast (women): monthly breast awareness from 18, clinical breast exam every 6 to 12 months from 25, and yearly mammogram and breast MRI starting at 30 to 35, or earlier based on family history
• Endometrium: education about symptoms from 35. Biopsy or ultrasound may be considered
• Colon: colonoscopy starting at 35 and every 5 years, or more often if polyps are found
• Kidney: imaging (ultrasound or MRI) every 1 to 2 years from 40
• Skin: yearly dermatology exam
• Children: yearly physical exam, thyroid ultrasound, and developmental and psychological assessment

Risk-reducing options include:

• risk-reducing mastectomy, discussed with a specialist
• hysterectomy after childbearing is complete
• removal of the thyroid if nodules are suspicious

Treatment of cancers follows standard approaches. Clinical trials of drugs targeting the PTEN pathway (such as mTOR inhibitors) are ongoing.

Family implications

PHTS is autosomal dominant: each child of an affected person has a 50 in 100 chance of inheriting the variant. An estimated 10 to 45 in 100 cases arise from a new variant with no family history. Testing parents, siblings and children allows relatives to begin screening early. Prenatal testing and preimplantation genetic testing are options for those planning a family.

Frequently asked questions

What is PTEN hamartoma tumor syndrome?

It is an inherited condition caused by a change in the PTEN gene. It causes benign growths in the skin, gut and other organs, a large head size, and higher risks of breast, thyroid, endometrial, kidney and colorectal cancers and melanoma.

Is Cowden syndrome the same as PTEN hamartoma tumor syndrome?

Cowden syndrome is one form of PTEN hamartoma tumor syndrome, usually diagnosed in adults. PHTS is the umbrella term that also includes Bannayan-Riley-Ruvalcaba syndrome and other PTEN-related conditions.

What cancers are linked to a PTEN mutation?

The main cancers are breast, thyroid (especially follicular), endometrial, kidney and colorectal cancers and melanoma. Regular screening, starting earlier than for the general population, helps detect these early.

How is PTEN syndrome diagnosed?

Doctors look for typical features such as a large head, skin lesions, gut polyps and early cancers, then confirm the diagnosis with a genetic test for PTEN variants, usually with genetic counseling.

Is PTEN hamartoma tumor syndrome inherited?

Yes, in an autosomal dominant pattern. Each child of an affected parent has a 50 in 100 chance of inheriting it. Some people have a new variant that was not inherited. Relatives should be offered testing.