Synonyms: polyposis, hamartomatous intestinal polyps-and-spots syndrome.

Peutz-Jeghers syndrome is an autosomal dominant disorder characterised by mucosal pigmentation of the lips and gums with multiple intestinal hamartomatous polyps and an increased risk of various cancers compared to the general population.

The syndrome is co-named after Peutz, who in 1921 first recognised the association of gastrointestinal (GI) polyposis and mucocutaneous pigmentation, and Jeghers, who wrote the definitive descriptive reports and drew more wide-spread attention to the condition in 1949.¹

Epidemiology

• Peutz-Jeghers syndrome is rare with a prevalence of about 1/50,000.²
• Autosomal dominant condition with high penetrance.
• In up to two thirds of cases, mutations can be identified in the serine/threonine kinase gene STK11(LKB1) on chromosome 19 (19p13.3).³ STK11 is thought to be a tumour suppressor gene.

Presentation

• Family history: asymptomatic but requesting investigation/counselling.
• Deeply pigmented lesions on the lips (cross the vermillion border) and buccal mucosa. May also be present on hands and feet (particularly palms and soles) and around anus and genitalia. These lesions may be most prominent in infancy and fade after puberty.
• Repeated bouts of abdominal pain in a young patient (due to obstruction or intussusception).
• Unexplained intestinal bleeding in a young patient or iron-deficiency anaemia.
• Rectal prolapse.
• Precocious puberty.
• Nasal, bronchial, biliary tract, uterine or bladder polyps.

Investigations

• Full blood count: may show anaemia.
• Iron studies may show iron deficiency.
• Faecal occult blood tests to check for GI bleeding.
• Endoscopy: small bowel follow-through or capsular endoscopy;⁴ colonoscopy to determine presence and location of intestinal polyps.
• Genetic analysis.

Management

• If Peutz-Jeghers syndrome is suspected on the basis of clinical criteria, the patient should be referred to a regional genetics centre for formal counselling and mutation analysis of the relevant gene.²
• Surgical excision of lesions may be required:
  • Endoscopic polypectomy for diagnosis and control of symptoms.
  • Laparotomy and resection are reserved for repeated intussusception or persistent intestinal bleeding.⁵

Surveillance

Benefits of surveillance are uncertain but cancer risk is high so current recommendations (British Society of Gastroenterology) are:²

• Colonoscopy or flexible sigmoidoscopy from age 18 years at 3-yearly intervals.
• Oesophagogastroduodenoscopy (OGD) from age 25 years at 3-yearly intervals.

Members of the family of an affected family where a causative gene has been identified should be referred for gene counselling and predictive gene testing. Where they test negative, there is no indication for their continued surveillance.²

Complications

• High cancer risk:
  • Almost 50% of patients with Peutz-Jeghers syndrome develop and die from cancer by age 57 years.¹
  • Most common cancers are gastroesophageal, small bowel, colorectal and pancreatic.
  • Also risk of ductal breast cancer, thyroid, lung, uterine, Sertoli cell testicular tumours or ovarian sex cord tumours.
  • The cancer-susceptibility is thought to arise from mutation activating serine/threonine kinase.
• Gastrointestinal bleeding
• intussusception
• Rectal prolapse
• Adhesions and obstructions from repeated operations

Prognosis⁶