Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC/Lynch syndrome)

  • Inheritance pattern
    • Autosomal dominant
    • Homozygous or compound heterozygous
  • Mutation
    • Germline mutations in the MMR pathway genes
      • MLH1 (mutL homolog 1)
      • MSH2 (mutS homolog 2)
      • MSH6 (mutS homolog 6)
      • PMS2 (PMS1 homology 2)
      • EPCAM
    • Defects in mismatch repair (MMR) mechanisms → microsatellite instability
    • Inability for MMR machinery to identify and excise DNA damage
  • Clinical presentation
    • Childhood onset
    • Broad spectrum malignancy
      • Aumento de risco de adenomas colorectais com 80% de risco de progressão para carcinoma
    • Cutaneous phenotype
      • Pigmentary: CALMs, hyper- and hypopigmentation, irregular dermal melanocytosis → “mild NF phenotype”
        • At least one CALM or hyperpigmented skin area is found in more than 60% of patients
      • Venous anomalies
      • Pilomatricomas
    • Mild immunodeficiency due to low IgG and IgA
 
Variants
Muir-Torre Syndrome