PTEN Hamartoma Tumor Syndrome (PHTS)

PTEN Hamartoma Tumor Syndrome (PHTS)

• Gene Clinics Entry
• Includes Cowden Syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome (PLS)
• Diagnosis only if PTEN mutation present
  • PTEN functions as a tumor suppressor gene, by inhibiting PI3K pathway (please see growth factors page)
  • Proportion of PTEN mutation present in above syndromes: CS (80%), BRRS (60%), PLS (50%), PS (20%)
  • If PTEN mutation absent, then patients classified under corresponding clinical syndrome
• Autosomal dominant

Cowden syndrome

• Part of PTEN Hamartoma Tumor Syndrome
• Formation of skin lesions, hamartomas and neoplastic growths, throughout multiple body systems (therefore also known as multiple hamartoma syndrome)
• Clinical criteria (pathognomic, or 2+ major, or 4+ minor, or combinations):
  • Pathognomonic: Cerebellar dysplastic gangliocytoma (adult Lhermitte-Duclos disease) or mucocutaneous lesions (facial trichilemmomas, acral keratoses, papillomatous lesions, or mucosal lesions
  • Major: Breast cancer, thyroid cancer (non-medullary), endometrial cancer, macrocephaly,
  • Minor: Benign thyroid lesions (e.g., adenoma, multinodular goiter), mental retardation (IQ less than or equal to 75), hamartomatous intestinal polyps, fibrocystic disease of the breast, lipomas, fibromas, GU tumors (especially renal cell carcinoma), GU malformation, uterine fibroids
• Autosomal dominant
• Clinical manifestation: by 30s 99% develop the mucocutaneous stigmata; colon polyps typically minute and asymptomatic
• Tumor risk:
  • Breast CA: lifetime risk 25-50%; average age 38-46
  • Thyroid CA: lifetime risk 10%
  • Endometrial CA: lifetime risk 5-10%
• Prevalence: 1/200,000 but likely higher due to often subtle external manifestations