Peutz Jeghers syndrome and the STK11 gene

Peutz Jeghers syndrome and the STK11 gene

Peutz Jeghers syndrome (pronounced (pootz-JAY-gerz) is a hereditary cancer syndrome caused by germline mutations in the STK11 gene (pronounced: S T K eleven). It is a rare syndrome, affecting 1 in 50,000 to 1 to 200,000 people.

Peutz Jeghers syndrome is characterised by polyps called hamartoma which occur in the digestive tract, especially the small and large intestines, and freckling (hypermelanotic spots) around the mouth as well as inside the mouth.

Individuals with Peutz Jeghers syndrome are at increased risk of cancer, particularly of the large and small intestine, stomach, pancreas, breast and ovary. These cancers can occur at a young age. Tumours which secrete oestrogen, involving the ovary or testes, can also occur.

An individual has a 90% chance of carrying an STK11 germline mutation if they meet the clinical diagnosis of Peutz Jeghers syndrome:

  • 2 or more PJS-related hamartomatous polyps.
  • any number of PJS-related hamartomatous polyps AND mucocutaneous pigmentation.
  • either a hamartomatous polyp or mucocutaneous pigmentation AND a family history of Peutz Jeghers syndrome.

Note: PJS related polyps have characteristic histopathology of smooth muscle bundles with arborising (branching tree) appearance.

Most people with an STK11 mutation and Peutz Jeghers syndrome have freckling (actually dark blue to dark brown macules referred to as mucocutaneous pigmentation) on the lips and inside the mouth. While freckles are very common, it is very unusual to have many on the lips or inside the mouth. These dark macules appear in childhood but may fade as a person gets older. They also occur around the nostrils and the finger nails. They don't become cancerous.

More than one third of people with Peutz Jeghers syndrome have no family history of polyps or mucocutaneous pigmentation. Also, not all individuals with dark spots on the lips and in the mouth have Peutz Jeghers syndrome. Laugier–Hunziker syndrome is an example of acquired pigmentation and no polyps occur.

Management of Peutz Jeghers syndrome

Because hamartomatous polyps can grow large and bleed and may cause bowel blockages (intussusception) in children, screening starts at age 8:

  • Annual blood test to check for anaemia.
  • endoscopy and colonoscopy to screen the stomach, duodenum and colon.
  • video capsule endoscopy (VCE) or magnetic resonance endoscopy (MRE) to screen the small intestines.

If no polyps are found, the screening restarts at age 18, occurring every 3 years or as determined by polyp load.

Management of cancer risk in Peutz Jeghers syndrome

Men and women are at increased risk for pancreatic cancer. This risk may be 10% over a lifetime.

It is not yet known whether screening for pancreatic cancer is helpful (by finding the cancers early) or harmful (due to investigations and even surgery for things that turn out not to be cancer). Patients are encouraged to enrol in research studies.

For women with Peutz Jeghers syndrome

Women with PJS have a high risk of breast cancer (~45% lifetime risk). Breast screening, with annual breast MRIs, should start at age 30. Some women choose to have the breast tissue removed (bilateral mastectomies), reducing the risk to less than 1%.

There is an increased risk of cervical cancer. It is a rare but aggressive form that is NOT caused by the Human Papilloma Virus (HPV). Guidelines recommend review by a gynaecologist with an endocervical smear annually from 18 years of age.

Women and girls with Peutz Jeghers syndrome can develop a benign growth of the ovaries (a sex cord tumour with annular tubules or SCTAT). These growths can secrete oestrogen and can cause early puberty or menstrual problems.

For men with Peutz Jeghers syndrome

Men also develop oestrogen secreting tumours. These are large calcifying Sertoli cell tumors (LCST) of the testes. If untreated, the excess oestrogen can result in gynecomastia (breast tissue development), feminisation and if LCST occurs before puberty, advanced skeletal age and short stature. LCST usually present as a lump in the testicle.

Does this sound like you or your family?

Has Peutz Jeghers syndrome been diagnosed or an STK11 mutation been detected in you or a blood relative?

Make an appointment with Dr Hilda High at Sydney Cancer Genetics. It is a confidential opportunity to discuss your personal and family history of cancer. Genetic testing can be organised and will be bulk billed if you meet the Medicare testing criteria.

These links may be useful

  • The Peutz-Jeghers Syndrome Online Support Group is a support group for individuals and families affected by Peutz-Jeghers syndrome. It is based in the USA but has members worldwide.
  • The Cancer Genetics section of the Cancer Institute's eviQ website provides up-to-date Australian-based management guidelines