What are the clinical features of Peutz-Jeghers syndrome?

Clinical Features of Peutz-Jeghers Syndrome

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by distinctive mucocutaneous melanin pigmentation and hamartomatous polyps throughout the gastrointestinal tract, with a 93% lifetime risk of developing cancer. 1

Key Diagnostic Features

Mucocutaneous Pigmentation

• Present in >95% of affected patients 1
• Dark brown or blue-brown melanotic pigmented macules (1-5 mm in size)
• Typically appears in infancy and may fade during late adolescence 2
• Distribution pattern:
  • Vermilion border of the lips (94% of patients)
  • Buccal mucosa (66%)
  • Hands (74%)
  • Feet (62%)
  • Periorbital, perianal, and genital regions 1
• Important distinction: Unlike freckles, PJS pigmentation occurs on the buccal mucosa and around nostrils/mouth 2

Gastrointestinal Hamartomatous Polyps

• True hamartomas with unique histopathologic characteristics:
  • Frond-like structure
  • Branching framework of connective tissue and smooth muscle
  • Lined by normal intestinal epithelium rich in goblet cells
  • Elongated and convoluted glands with arborizing growth pattern 2
• Distribution:
  • Small intestine (64%)
  • Colon (64%)
  • Stomach (49%)
  • Rectum (32%) 1

Common Complications

• Gastrointestinal bleeding (acute or chronic)
• Small bowel intussusception
• Intestinal obstruction 3, 4
• These complications often require emergency surgical intervention 5

Genetic Basis

• Caused by germline mutations in the STK11/LKB1 gene on chromosome 19p13.3
• STK11 functions as a tumor suppressor gene encoding a serine/threonine kinase
• Mutations detected in 66-94% of PJS cases 1
• Inheritance pattern: autosomal dominant with incomplete penetrance and variable expression 2

Cancer Risk

• Overall relative risk: 15.2 times the general population
• Lifetime risk of any cancer by age 64: 93%
• Cumulative cancer risk by age 70: 81% 1
• Specific cancer risks by age 70:
  • Breast (54%)
  • Colon (39%)
  • Pancreas (36%)
  • Stomach (29%)
  • Ovary (21%)
  • Lung (15%)
  • Small intestine (13%)
  • Cervix (10%)
  • Uterus (9%)
  • Testes (9%) 1
• Rare but characteristic tumors:
  • Sex-cord tumors with annular tubules of the ovary
  • Adenoma malignum of the cervix
  • Testicular tumors of sex-cord and Sertoli-cell type 1, 3

Diagnostic Criteria

PJS diagnosis can be made in patients with:

• Histologically confirmed hamartomatous polyp(s) plus at least 2 of the following:
  • Labial melanin deposits
  • Family history of the syndrome
  • Small bowel polyposis 2, 1

Clinical Pitfalls to Avoid

• Misdiagnosis is common - patients often visit hospitals repeatedly before correct diagnosis 5
• Melanotic spots on the face may be overlooked, leading to missed diagnosis 5
• Differential diagnosis should include Laugier-Hunziker syndrome, which has similar pigmentation but:
  • Lesions appear in young/middle-aged adults (not infancy)
  • Less periorificial pigmentation
  • May have conjunctival pigmentation and longitudinal melanonychia 2
• PJS has equal distribution between males and females and occurs in all racial groups, with estimated incidence of 1/50,000 to 1/200,000 live births 2, 1

Early recognition of these characteristic features is crucial for timely diagnosis, appropriate management, and cancer surveillance to reduce morbidity and mortality in affected individuals.