The Frequency of Muir-Torre Syndrome Among Lynch Syndrome Families

• Published in: JNCI : Journal of the National Cancer Institute Vol. 100; no. 4; pp. 277 - 281
• Main Authors: South, Christopher D., Hampel, Heather, Comeras, Ilene, Westman, Judith A., Frankel, Wendy L., de la Chapelle, Albert
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 20-02-2008; Oxford Publishing Limited (England)
• Subjects: Biological and medical sciences; Cohort Studies; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Dermatology; DNA Mismatch Repair; Families & family life; Genes; Genetic Predisposition to Disease; Genetic research; Germ-Line Mutation; Humans; Incidence; Medical sciences; Mutation; MutS Homolog 2 Protein - genetics; Oncology; Skin cancer; Skin Neoplasms - genetics; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; United States; North America; America; Human; Skin disease; Hereditary nonpolyposis colorectal cancer; Rectal disease; Family study; Malignant tumor; Epidemiology; Genetic disease; Skin cancer; Repair gene; Colonic disease; Muir-Torre syndrome; Cancerology; Cohort study; Deletion; Genetics; Digestive diseases; Intestinal disease; Frequency; Public health; Cancer
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/djm291

Lynch syndrome is the predisposition to visceral malignancies that are associated with deleterious germline mutations in DNA mismatch repair genes, including MLH1, MSH2, MSH6, and PMS2. Muir-Torre syndrome is a variant of Lynch syndrome that includes a predisposition to certain skin tumors. We determined the frequency of Muir-Torre syndrome among 50 Lynch syndrome families that were ascertained from a population-based series of cancer patients who were newly diagnosed with colorectal or endometrial carcinoma. Histories of Muir-Torre syndrome–associated skin tumors were documented during counseling of family members. Muir-Torre syndrome was observed in 14 (28%) of 50 families and in 14 (9.2%) of 152 individuals with Lynch syndrome. Four (44%) of nine families with MLH1 mutations had a member with Muir-Torre syndrome compared with 10 (42%) of 24 families with MSH2 mutations (P = .302). Families who carried the c.942+3A>T MSH2 gene mutation had a higher frequency of Muir-Torre syndrome than families who carried other mutations in the MSH2 gene (75% vs 25%; P = .026). Muir-Torre syndrome was not found in families with mutations in the MSH6 or PMS2 genes. Our results suggest that Muir-Torre syndrome is simply a variant of Lynch syndrome. Screening for Muir-Torre syndrome–associated skin lesions among patients with Lynch syndrome is recommended.