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Background <p>Hereditary colorectal syndromes arise from defects in the DNA mismatch repair (MMR) system or defined germline mutations (APC, MUTYH), leading to accelerated adenoma formation and carcinogenesis in affected families. Clinically, they are characterized by early disease onset and high interval carcinoma rates.</p> Aim <p>Systematic overview of molecular pathomechanisms, clinical features, surveillance strategies, and treatment options for hereditary colorectal syndromes.</p> Methods <p>Systematic literature search, evaluation of German and European guidelines and analysis of relevant treatment studies.</p> Results <p>The MMR gene defects (MLH1, MSH2, MSH6, PMS2) drive microsatellite instability (MSI)-high tumors with a high mutational burden. Mutations in the adenomatous polyposis coli gene (APC, FAP/AFAP) and biallelic MUTYH mutations (MAP) lead to familial adenomatous polyposis syndromes. If the family history meets the Amsterdam I/II or Bethesda criteria, MSI screening via immunohistochemistry and genetic testing is warranted. For confirmed hereditary colorectal syndrome, a structured endoscopic surveillance is recommended (Lynch syndrome: annual colonoscopy over age&#xa0;25 years, FAP annually from ages&#xa0;10–12 years, AFAP: over age&#xa0;15 years, MAP over age&#xa0;18 years, upper gastrointestinal endoscopy based on the Spigelman score). The MSI-high colon cancers respond to modern checkpoint inhibitors (PD-1/CTLA-4), partially with notably high complete remission rates. Surgical treatment with confirmed cancer HNPCC segmental oncological resection, FAP proctocolectomy with ileoanal pouch, AFAP/MAP colectomy.</p> Discussion <p>An early, genotype-guided, interdisciplinary management combining rational diagnostics, structured surveillance and modern surgical and systemic treatment nowadays significantly improves the prognosis of patients.</p>

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Management hereditärer kolorektaler Syndrome

  • 期刊论文

  • 发表日期：

    2025年10月2日

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  • Nicolai Härtel,
  • Mario Kaufmann,
  • Christoph Reißfelder

摘要

Background

Hereditary colorectal syndromes arise from defects in the DNA mismatch repair (MMR) system or defined germline mutations (APC, MUTYH), leading to accelerated adenoma formation and carcinogenesis in affected families. Clinically, they are characterized by early disease onset and high interval carcinoma rates.

Aim

Systematic overview of molecular pathomechanisms, clinical features, surveillance strategies, and treatment options for hereditary colorectal syndromes.

Methods

Systematic literature search, evaluation of German and European guidelines and analysis of relevant treatment studies.

Results

The MMR gene defects (MLH1, MSH2, MSH6, PMS2) drive microsatellite instability (MSI)-high tumors with a high mutational burden. Mutations in the adenomatous polyposis coli gene (APC, FAP/AFAP) and biallelic MUTYH mutations (MAP) lead to familial adenomatous polyposis syndromes. If the family history meets the Amsterdam I/II or Bethesda criteria, MSI screening via immunohistochemistry and genetic testing is warranted. For confirmed hereditary colorectal syndrome, a structured endoscopic surveillance is recommended (Lynch syndrome: annual colonoscopy over age 25 years, FAP annually from ages 10–12 years, AFAP: over age 15 years, MAP over age 18 years, upper gastrointestinal endoscopy based on the Spigelman score). The MSI-high colon cancers respond to modern checkpoint inhibitors (PD-1/CTLA-4), partially with notably high complete remission rates. Surgical treatment with confirmed cancer HNPCC segmental oncological resection, FAP proctocolectomy with ileoanal pouch, AFAP/MAP colectomy.

Discussion

An early, genotype-guided, interdisciplinary management combining rational diagnostics, structured surveillance and modern surgical and systemic treatment nowadays significantly improves the prognosis of patients.