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

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Abstract

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
Volume1
Issue number2
StatePublished - 2001

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DNA Mismatch Repair
Colorectal Neoplasms
Germ-Line Mutation
Polyps
Adenoma
Lymphoma
Neoplasms
Neurocutaneous Syndromes
Genes
Mutation
Neurofibromatoses
Glioblastoma
Brain Neoplasms
Leukemia
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Trimbath, J. D., Petersen, G. M., Erdman, S. H., Ferre, M., Luce, M. C., & Giardiello, F. M. (2001). Café-au-lait spots and early onset colorectal neoplasia: A variant of HNPCC? Familial Cancer, 1(2), 101-105.

Café-au-lait spots and early onset colorectal neoplasia : A variant of HNPCC? / Trimbath, Jill D.; Petersen, Gloria M; Erdman, Steven H.; Ferre, Merry; Luce, Michael C.; Giardiello, Francis M.

In: Familial Cancer, Vol. 1, No. 2, 2001, p. 101-105.

Research output: Contribution to journalArticle

Trimbath, JD, Petersen, GM, Erdman, SH, Ferre, M, Luce, MC & Giardiello, FM 2001, 'Café-au-lait spots and early onset colorectal neoplasia: A variant of HNPCC?', Familial Cancer, vol. 1, no. 2, pp. 101-105.
Trimbath JD, Petersen GM, Erdman SH, Ferre M, Luce MC, Giardiello FM. Café-au-lait spots and early onset colorectal neoplasia: A variant of HNPCC? Familial Cancer. 2001;1(2):101-105.
Trimbath, Jill D. ; Petersen, Gloria M ; Erdman, Steven H. ; Ferre, Merry ; Luce, Michael C. ; Giardiello, Francis M. / Café-au-lait spots and early onset colorectal neoplasia : A variant of HNPCC?. In: Familial Cancer. 2001 ; Vol. 1, No. 2. pp. 101-105.
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title = "Caf{\'e}-au-lait spots and early onset colorectal neoplasia: A variant of HNPCC?",
abstract = "Background: Caf{\'e}-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: Caf{\'e}-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.",
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T1 - Café-au-lait spots and early onset colorectal neoplasia

T2 - A variant of HNPCC?

AU - Trimbath, Jill D.

AU - Petersen, Gloria M

AU - Erdman, Steven H.

AU - Ferre, Merry

AU - Luce, Michael C.

AU - Giardiello, Francis M.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Café-au-lait spots

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KW - Hereditary nonpolyposis colorectal cancer (HNPCC)

KW - Mismatch repair genes

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