Colorectal cancer tends to aggregate in families. A small fraction of these families have adenomatous polyposis coli caused by inherited mutations in the APC gene on chromosome 5q [1]. Hereditary nonpolyposis colon cancer is more common although heterogeneous and difficult to define [2]. We recently identified a family with exceptionally prominent features of the Muir-Torre syndrome, a clinically distinct form of hereditary nonpolyposis colon cancer characterized by sebaceous neoplasms of the skin and associated with cancers of the colon, rectum, and genitourinary tract [3].

View larger version (24K): [in this window] [in a new window]   Figure 1. Condensed pedigree of three generations (I to III) of the family. Patients II-2 and II-3 had four and six primary colorectal carcinomas, respectively, as well as other forms of cancer. Squares = men, circles = women, diamonds = persons of either sex.

Patient II-3 developed at least nine primary cancers of the stomach, duodenum, jejunum, colon, and rectum during a 29-year period. In addition, several villous adenomas of the colon and two cutaneous sebaceous adenomas were excised. Cancers in patients with the Muir-Torre syndrome are reported to have an indolent course, even after metastases have developed [3]. The syndrome occurs in an autosomal dominant pattern in some families, but clustering of multiple primary cancers among several relatives is rare. To confirm the diagnosis of the Muir-Torre syndrome, dermatologic consultation was requested for our proband and his cousin (patient III-15). Skin biopsy specimens showed previously unsuspected sebaceous adenomas in both patients.

Sebaceous adenoma identifies the subset of families with hereditary nonpolyposis colon cancer who have the Muir-Torre syndrome and those at increased cancer risk. These family members should be monitored to detect early cancers and perhaps should be enrolled in chemoprevention trials. Genetic studies can help identify the inherited molecular defect that causes the Muir-Torre syndrome.