The Muir-Torre syndrome: a rare variant of hereditary nonpolyposis colorectal cancer associated with hMSH2 mutation

The Muir-Torre syndrome is a rare autosomal dominant disorder characterized by the association of visceral malignancies with typical skin lesions. This syndrome is now considered a subtype of the more common hereditary nonpolyposis colorectal cancer syndrome (HNPCC). This last condition has been ascribed to mutations in four mismatch repair genes, and similar mutations, mostly located at hMSH2 gene, are now being described in some Muir-Torre patients. We describe the case of a 64-yr-old woman with no family history of colorectal cancer, who developed two visceral malignancies belonging to the usual spectrum of hereditary nonpolyposis colorectal cancer (colon and stomach), beginning at age 41. She additionally developed several skin tumors, including multiple keratoacanthomas, thus fulfilling Muir-Torre diagnostic criteria. Because of her cutaneous phenotype, she was screened for DNA mismatch repair gene mutations by in vitro synthetized protein assay (IVSP) and a truncating mutation was identified at hMSH2. We further discuss the clinical significance of the Muir-Torre phenotype, the association of this syndrome with hMSH2 mutations and the important implications of genetic diagnosis for the patient and her offspring.