What is Peutz-Jeghers syndrome?

Peutz-Jeghers syndrome is a disease caused by mutations – or genetic changes – in the STK11 gene. It is characterized by the occurrence of polyps in the gastrointestinal tract and typical pigment spots on the skin and mucous membranes. In addition, there is also an increased risk of cancerous diseases.

How is Peutz-Jeghers syndrome diagnosed?

Suspected Diagnosis

Peutz-Jeghers syndrome is suspected with presentation of the following:

  • ≥ 2 polyps of the Peutz-Jeghers-syndrome type (PJS type) in the gastrointestinal tract

  • Characteristic dark-blue to dark-brown pigment spots on the skin or mucous membranes

  • Enlargement of the mammary gland in men as a result of estrogen-producing testicular tumors

  • At first invagination (the telescoping of one section of the intestine into another), especially in children or young adults

Genetic Diagnostics

The diagnosis of “Peutz-Jeghers syndrome” is confirmed by detection of a mutation – or genetic change – in the STK11 gene.

Diagnostic Criteria

The diagnosis of “Peutz-Jeghers syndrome” is confirmed by detection of a mutation in the STK11 gene or one of the following findings:

  • ≥ 2 histologically verified PJS-type polyps

  • Any number of PJS-type polyps in a person who has at least one close relative with PJS

  • Characteristic dark-blue to dark-brown pigmentation in the skin or mucous membranes of a person who has at least one close relative with PJS

  • Any number of PJS-type polyps in a person with characteristic dark-blue to dark-brown pigmentation

What is the risk of cancer?

What is characteristic of Peutz-Jeghers syndrome is that polyps in the gastrointestinal tract and typical dark-blue to dark-brown pigmentation in the skin and mucous membranes appear at the same time. The risk of malignant diseases inside and outside of the gastrointestinal tract is considerably higher.

Cancerous Diseases

The following table shows the risk and average age of malignant diseases known to be associated with Peutz-Jeghers syndrome.

Manifestation Location Risk Manifestation Age
Large intestine 39% 42 – 46 years
Stomach 29% 30 – 40 years
Small intestine 13% 37 – 42 years
Breast 32% – 54% 37 – 59 years
Ovary 21% 28 years
Cervix 10% 34 – 40 years
Uterus 9% 43 years
Pancreas 11% – 36 % 51 – 52 years
Testicles 9 % 6 – 9 years
Lungs 7% – 17 % 47 years

Polyps

While polyps can develop throughout the gastrointestinal tract, they are most commonly found in the small intestine. Polyps can occur outside of the gastrointestinal tract as well (renal pelvis, urinary bladder, ureters, lungs, nose, and gall bladder). Their potential to be malignant remains to be characterized. The polyps can cause complications such as intestinal obstructions, rectal prolapse, or severe gastrointestinal bleeding. The average age when the first symptoms appear is 10 years, with polyps first removed (polypectomy) at the age of 13 on average.

Mucocutaneous Pigmentation

It is rare for the characteristic dark-blue to dark-brown pigment spots to exist at birth already; they typically develop by age 5. The pigmentation fades during puberty and adulthood. The spots mainly occur around the mouth, on the eyes, nostrils, and inner cheek, and around the anal region. Pigment spots on the fingers are also common. No risk of cancer is associated with these characteristic pigmentations.

Gonadal tumors

Female PJS patients have an increased risk of tumors in the ovaries and fallopian tubes. They generally occur on both sides and have a benign progression.

Male PJS patients have an increased risk of testicular tumors. These tumors can secrete estrogen and are generally benign.

What causes Peutz-Jeghers syndrome?

Peutz-Jeghers syndrome is caused by a mutation – or genetic change – in the STK11 gene. This gene encodes for the STK11 protein, which is a tumor suppressor, meaning that it suppresses the development of tumor cells. Now if the STK11 gene is altered, the STK11 protein will not be produced correctly and will be unable to function as a tumor suppressor. This leads to the development of polyps and tumors.

Peutz-Jeghers syndrome is usually passed on by parents to their children. In these cases, it is inherited as an autosomal dominant disease. The remaining cases (around 25%) are due to a spontaneous or new mutation, called a de novo mutation.

Is there a treatment?

Polyps > 1 cm in size should be removed as a precaution to prevent long-term complications and reduce the risk of progressing into a malignant tumor.

Malignant diseases should be treated according to the pertinent protocols.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

Gastrointestinal Tract

  • Gastroscopy, video capsule endoscopy, or magnetic resonance enterography and colonoscopy at 8 years of age (or earlier if symptoms occur)

    • If there are polyps -> repeat every 3 years
    • If there are no polyps -> repeat at the age of 18

Gonads, Breasts, Ovaries, Uterus, and Cervix

  • Annual clinical examination, particularly with regard to enlarged mammary glands or space-occupying lesions of the testicles in boys and premature puberty in girls from birth to adolescence

  • Annual breast cancer screening from 25 years of age

  • Annual gynecological examination with an ultrasound and blood test (CA125 in the serum) from 18-20 years of age

Pancreas

  • Magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound every 1-2 years from the age of 30

Self-Care and Support

What should I pay special attention to?

People with this tendency to develop colon cancer should be cared for at a center that provides surveillance screening.

Regardless of any surveillance examinations, you should see a doctor as soon as you develop symptoms in the gastrointestinal tract. They may involve blood or mucous in the stool, stool anomalies such as diarrhea or constipation, flatulence, or pain. Even non-specific signs such as weight loss should be paid attention to and reported to a doctor so that he or she can check whether you have colon cancer.

You should also see a doctor right away if you notice any other newly occurring abnormalities or symptoms, such as abdominal or lower abdominal pain or palpable nodules in the breast.

Support Groups and Additional Information