Café-au-lait spots and early onset colorectal neoplasia: A variant of HNPCC?

Jill D. Trimbath, Gloria M. Petersen, Steven H. Erdman, Merry Ferre, Michael C. Luce, Francis M. Giardiello

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Background: Café-au-lait spots (CALS) are classically found in neurocutaneous syndromes such as neurofibromatosis, but have not been associated with hereditary colorectal cancer. However, review of hereditary colorectal cancer case reports reveals occasional description of CALS on physical exam. Methods: We describe the colonic and extracolonic phenotype in a family with CALS and early onset colorectal neoplasia (adenomas and/or cancer) and review 23 additional families reported in the literature. Results: Among the 24 families, 32/59 (54.2%) individuals had colorectal adenomas diagnosed at a mean age of 15.7 ± 1.1 (SE) years (range 5-38 years). The majority (24/32, 75.0%) of persons at first colorectal examination had oligopolyposis (<100 polyps) versus polyposis (≥ 100 polyps). Forty-two of 59 (71.2%) individuals were affected with colorectal cancer, diagnosed at a mean age of 31.9 ± 2.7 years (range 5-70 years). A brain tumor was found in 28/59 (47.5%) affected individuals (4 families with 2 or more cases) with an overall mean age of diagnosis of 16.5 ± 1.2. Lymphoma and/or leukemia was found in 8/24 (33.3%) families (one family with 3 cases). Two families had mutation of the mismatch repair gene, hPMS2 (1 with homozygous germline mutation), while two carried homozygous germline mutations of another mismatch repair gene, hMLH1. Conclusions: Café-au-lait spots with early onset colorectal neoplasia may identify families with a variant of HNPCC characterized by oligopolyposis, glioblastoma at young age, and lymphoma. This variant may be caused by homozygous mutation of the mismatch repair genes, such as hPMS2 or hMLH1.

Original languageEnglish (US)
Pages (from-to)101-105
Number of pages5
JournalFamilial Cancer
Issue number2
StatePublished - 2001


  • Café-au-lait spots
  • Colon cancer
  • Colon polyps
  • Hereditary nonpolyposis colorectal cancer (HNPCC)
  • Mismatch repair genes

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Genetics(clinical)
  • Cancer Research


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