Peutz-Jeghers syndrome (STK11): polyps, freckling and cancer risk

Peutz-Jeghers syndrome (PJS) combines two features. One is a particular type of non-cancerous bowel polyp known as a hamartomatous polyp. The other is dark pigmentation on the skin and inside the mouth. A third element is an increased chance of cancers, mainly of the gut, breast, pancreas and reproductive organs.

The NHS Genomics Education Programme says the polyps can occur anywhere in the digestive tract but are most often in the small intestine, particularly the jejunum. The age at which they cause trouble varies, and some children have symptoms within the first few years of life. Cancer Research UK also notes that signs can appear during childhood, including darker skin around the mouth, lips, fingers and toes, and freckling around and inside the mouth.

Because the pigmentation is often the first visible clue, doctors sometimes recognise the condition from a child's lips and mouth. The spots are melanocytic macules, dark blue to dark brown. They commonly develop in childhood and fade in puberty and adulthood, so their absence in an adult does not exclude the diagnosis.

The more serious early problems come from the polyps. A polyp can act as a lead point so that the bowel telescopes into itself, causing sudden colicky abdominal pain and vomiting. The programme gives the risk of this intussusception as 50% by 20 years of age, and it is the most common way that PJS comes to attention in childhood. Slow bleeding from polyps can cause anaemia.

• Dark spots on the lips, inside the cheeks, around the eyes and nostrils, and on fingers and toes.

• Repeated abdominal pain, which may be a sign of a polyp causing blockage.

• Tiredness and pallor from anaemia caused by hidden bleeding.

• Sudden severe abdominal pain with vomiting needs urgent medical attention: call NHS 111, or 999 if severe.

A clinical diagnosis can be made when a person has three or more histologically confirmed PJS-type polyps, or any number of such polyps together with a close relative who has PJS, or characteristic pigmentation with a close relative who has PJS, or polyps together with the typical pigmentation.

Genetic testing for STK11 is available under the National Genomic Test Directory and meets different criteria, for example two or more PJS-type polyps, a polyp with characteristic pigmentation, characteristic pigmentation under age 10, or particular rare tumours such as sex cord tumours with annular tubules. The programme cautions that these testing criteria do not exactly mirror the clinical criteria, so a person who meets clinical criteria but not testing criteria is discussed with a specialist team.

About 20% of harmful STK11 variants are deletions of the whole gene or part of it, which is why laboratories use methods that detect these as well as single-letter changes.

PJS follows an autosomal dominant pattern. A person who carries an STK11 variant has a 50% chance of passing it on to each child, and brothers and sisters of an affected person have the same chance. How severe the condition is varies a lot between families and even within one family, so a child may have a milder or more severe course than a parent.

The NHS Genomics Education Programme says predictive testing can be offered to children from three years of age, so that abdominal symptoms can be interpreted properly if they arise. This is earlier than for most adult-onset cancer genes because bowel obstruction can occur in childhood.

The NHS Genomics Education Programme reports a high cancer risk in PJS, about 55% by the age of 60, while cautioning that quoted figures may be inflated because people with more obvious disease were studied first and may be revised as testing finds milder cases. Sites most often affected include the gut, breast, pancreas, ovary, cervix and testes. Cancer Research UK lists breast, bowel, pancreatic, stomach and ovarian cancers.

Surveillance follows UK guidance. Upper gut endoscopy and colonoscopy are recommended at eight years of age; if polyps are found they are repeated every three years and polyps are removed to prevent complications. If the first examinations are clear, routine endoscopies resume from 18, or sooner if symptoms arise. Small bowel checks by video capsule endoscopy or MR enterography start at eight and are repeated every one to three years. Small bowel polyps larger than 1.5 to 2 cm, or smaller ones that cause symptoms, are considered for removal to prevent intussusception.

Women with PJS are advised to join the very high-risk breast screening programme from 30, which uses annual MRI or mammogram or both depending on age. The role of risk-reducing drugs or surgery is uncertain, and prophylactic mastectomy is not supported for an asymptomatic person without specific risk factors.

The condition often means repeated procedures from childhood, so continuity with a paediatric gastroenterology team and later an adult polyposis service helps. Families learn the warning signs of obstruction and know when a stomach ache needs urgent assessment.

The pigmentation tends to fade in puberty and adulthood. A genetic counsellor, who is part of the NHS pathway, can help with questions about family planning and sharing information with relatives. The NHS notes that counsellors can also direct families to patient support groups.