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Cancer syndromeCNS + colorectalOMIM 276300

Turcot syndrome

Mismatch repair cancer syndrome (Type 1) · constitutional mismatch repair deficiency (CMMRD) overlap

Turcot syndrome is a rare hereditary cancer-predisposition disorder characterised by colorectal adenomatous polyposis combined with primary central nervous system tumours. Two genetic forms are recognised: Type 1 (mismatch-repair gene mutations — Lynch syndrome variant — typically glioblastoma) and Type 2 (APC mutation — FAP variant — typically medulloblastoma). The skin-oncology relevance arises from overlap with sebaceous neoplasia (Muir-Torre spectrum in Type 1) and characteristic café-au-lait macules in constitutional mismatch repair deficiency (CMMRD).

CurrentLast reviewed 16 May 2026

Genetics

  • Type 1 (Mismatch Repair / Lynch variant):
    • Heterozygous (monoallelic) germline MMR gene mutation (MLH1, MSH2, MSH6, PMS2) — Lynch-associated; autosomal dominant.
    • Distinct from constitutional mismatch repair deficiency (CMMRD) — biallelic MMR loss, autosomal recessive, childhood-onset.
    • Typical CNS tumour: glioblastoma multiforme.
    • Overlap with Muir-Torre syndrome (sebaceous neoplasms).
  • Type 2 (APC / FAP variant):
    • Germline APC mutation (FAP).
    • Typical CNS tumour: medulloblastoma.
    • Overlap with classical FAP / Gardner syndrome (epidermoid cysts, osteomas, desmoids).
  • Both inherited as autosomal dominant; biallelic CMMRD is autosomal recessive.

Clinical features

  • Colorectal:
    • Multiple adenomas (fewer than classic FAP — typically 10-100).
    • Early-onset colorectal carcinoma.
  • CNS tumour:
    • Glioblastoma (Type 1) or medulloblastoma (Type 2).
    • Astrocytoma, ependymoma also reported.
  • Cutaneous features:
    • Type 1: sebaceous adenomas / carcinomas (Muir-Torre overlap), keratoacanthomas.
    • Type 2: epidermoid cysts, fibromas, lipomas, desmoids (FAP / Gardner).
    • CMMRD: multiple café-au-lait macules (NF1-like), axillary freckling, hypopigmented macules.
  • Other:
    • Type 2: papillary thyroid carcinoma, hepatoblastoma.
    • Type 1: endometrial, ovarian, ureteric / renal pelvis, gastric, small bowel.

Diagnosis

  • Clinical suspicion: combination of colonic polyposis + CNS tumour or family history.
  • Genetic testing:
    • R210 — Lynch / MMR genes (Type 1).
    • R206 — APC (Type 2).
    • R242 — CMMRD multi-gene panel.
  • Tumour MSI / MMR-IHC testing on colorectal / CNS specimen.
  • Cascade testing of family members.

Management and surveillance

  • Type 1 (Lynch variant):
    • Annual colonoscopy from age 20-25.
    • Annual gynae screening (endometrial / ovarian) from age 25-30.
    • Annual urinary cytology.
    • Annual brain MRI if family history of CNS tumour.
    • Annual dermatology review for sebaceous neoplasia.
  • Type 2 (FAP variant):
    • Colonoscopy / sigmoidoscopy from age 10-15 (per BSG FAP guideline).
    • Annual brain MRI if family history.
    • Annual thyroid USS.
    • Prophylactic colectomy in late teens / early 20s.
  • CMMRD: childhood-onset cancer; annual whole-body MRI; consider intervention trials.
  • Multidisciplinary: clinical genetics, GI, neurosurgery, dermatology, paediatric oncology (CMMRD).
  • Counsel about cancer-risk reduction: aspirin / smoking / lifestyle, family planning.

References

  1. Turcot J et al. Malignant tumors of the central nervous system associated with familial polyposis of the colon. Dis Colon Rectum. 1959;2:465-468.
  2. Hamilton SR et al. The molecular basis of Turcot's syndrome. N Engl J Med. 1995;332:839-847.
  3. Wimmer K et al. Diagnostic criteria for constitutional mismatch repair deficiency syndrome (CMMRD). J Med Genet. 2014;51:355-365.
  4. Monahan KJ et al. Guidelines for the management of hereditary colorectal cancer (BSG/ACPGBI/UKCGG). Gut. 2020;69:411-444.

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