Lynch syndrome

Lynch syndrome 

Updated: 11/03/2023

© Jun Wang, MD, PhD

General features

• Hereditary non-polyposis colorectal cancer
• Autosomal dominant
• Most common hereditary colorectal carcinoma syndrome
• 80% of patients develop colorectal carcinoma
• Increased risk of cancers of endometrium, ovaries, small bowel, stomach, upper urinary tract, and brain, or skin (Muir-Torre syndrome)

Genetic abnormalities

• Mismatch repair genes: MLH1, MSH2, MSH6, and PMS2 genes
• EPCAM: causing methylation and silencing of MSH2
  

MMRs

• MutSalpha: Heterodimer of MSH2 and MSH6, rocognizes base-pair mismatches
• MutLalpha: Heterodimer of MLH1 and PMS2, promote excision of mismatches
  

Diagnostic approach

• Screening test recommendations 
  • CRC diagnosed at age <50 years
  • Synchronous CRC, metachronous CRC, or Lynch syndrome-associated tumors
  • CRC with the MSI-H histology diagnosed at age <60 years
  • CRC in ≥1 first-degree relative with a Lynch syndrome-related tumor with 1 of the cancers diagnosed at age <50 years
  • CRC diagnosed in ≥2 first- or second-degree relatives with Lynch syndrome-related tumors
• Screening algorithm

Management

• Full colonoscopy every 1-2 years beginning at age 20-25 years
• Annual screening for endometrial cancer beginning at age 25-35
• Annual urinalysis and cytologic examination beginning at age 25
• Annual skin surveillance, and upper GI endoscopy beginning at age 35 when gastric cancer is part of the family
• At colonoscopic screening, patients have similar rate of adenomas as non-syndrome patients, but much higher incidence of carcinoma

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