Peutz-Jeghers syndrome

Introduction

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant genetic disorder characterised by the development of hamartomatous polyps in the gastrointestinal (GI) tract and mucocutaneous pigmentation. It carries a significantly increased risk of both GI and extra-GI malignancies.

Peak Incidence

• Most commonly diagnosed during childhood or adolescence.

Pathophysiology

• Caused by mutations in the STK11 (LKB1) tumour suppressor gene located on chromosome 19p13.3.
• Hamartomatous polyps are benign overgrowths of normal tissue but can cause mechanical complications (e.g. intussusception, obstruction).
• The genetic mutation predisposes to multiple cancers, often at a younger age than the general population.

Symptoms

• Gastrointestinal polyps:
  • May be asymptomatic.
  • Larger polyps can cause:
    • Abdominal pain.
    • Intermittent bowel obstruction.
    • Intussusception.
• GI bleeding symptoms:
  • Melena (dark, tarry stools from upper GI bleeding).
  • Haematochezia (bright red blood in stool from lower GI bleeding).
  • Anaemia from chronic blood loss.
• Mucocutaneous pigmentation:
  • Blue-black freckling typically on:
    • Lips and buccal mucosa.
    • Nostrils.
    • Palms, soles, fingers, toes.
    • Genital area.

Signs

• Mucocutaneous pigmentation (lentigines) – Often pathognomonic.
• Abdominal tenderness or distension – May suggest obstruction or intussusception.
• Pallor – Secondary to anaemia from chronic GI bleeding.

Diagnosis

• Clinical history:
  • Family history of PJS.
  • Early-onset GI symptoms, such as recurrent obstruction or anaemia.
• Endoscopic evaluation:
  • Colonoscopy and upper GI endoscopy to detect and monitor polyp burden.
  • Capsule endoscopy for small bowel visualisation.
• Genetic testing:
  • Identification of STK11 mutation confirms diagnosis.

Complications

• Increased lifetime cancer risk, including:
  • Colorectal cancer (~40–50% lifetime risk; often by age 45).
  • Small bowel, pancreatic, stomach, breast, ovarian, and testicular cancers.
• Recurrent bowel obstructions due to large or numerous polyps.
• Intussusception – A common complication in younger patients.
• Chronic iron-deficiency anaemia due to ongoing GI blood loss.

Management

Surveillance

• Begin from early adolescence.
• Routine screening every 2–3 years, including:
  • Colonoscopy.
  • Gastroscopy.
  • Capsule endoscopy (for small bowel polyps).
  • Consider additional organ-specific screening based on cancer risks (e.g. breast MRI, pancreatic imaging).

Polyp Management

• Endoscopic polypectomy – First-line for accessible and symptomatic polyps.
• Surgical resection – Considered when endoscopic removal is not feasible due to size, location, or polyp burden.

Specialist Involvement

• Gastroenterology – For surveillance, endoscopic therapy, and GI symptom management.

• Oncology – For cancer risk assessment and early detection programmes.

• Genetic counselling – Essential for affected individuals and family members to discuss inheritance, testing, and screening.