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Clinical features and diagnosis of Lynch syndrome (hereditary nonpolyposis colorectal cancer)


Lynch syndrome, also called hereditary nonpolyposis colorectal cancer (HNPCC), is the most common of the inherited colon cancer susceptibility syndromes. The use of the name HNPCC can be misleading in that this disorder predisposes to colon cancer and a variety of other cancers. As a result, the previously used name Lynch syndrome (after Dr. Henry Lynch, who did much to characterize and emphasize the importance of this familial syndrome) is being used more commonly.

Lynch syndrome is an autosomal dominant disorder that is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes. It accounts for 2 to 3 percent of all colon cancer cases and similarly is responsible for about 2 percent of endometrial cancers. Lynch syndrome is characterized by significantly increased risk for colon cancer and endometrial cancer as well as a smaller risk of several other associated cancers.

The clinical manifestations, diagnostic criteria, and genetics of Lynch syndrome will be reviewed here. Surveillance and screening strategies for Lynch syndrome are discussed separately. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Screening and management of patients and families".)

The American Gastroenterological Association (AGA) guideline for hereditary colorectal cancer and genetic testing [1], as well as other AGA guidelines, can be accessed through the AGA web site at


Patients with Lynch syndrome have a markedly increased risk of colorectal cancer (picture 1), endometrial cancer, and several other cancers including ovarian, upper urologic tract, gastric, small bowel, biliary/pancreatic, skin (sebaceous adenomas and carcinomas and keratoacanthomas), and brain cancers. The cancer risk in Lynch syndrome varies depending on geographic/environmental factors (for example, gastric cancer is a more common Lynch-associated cancer in countries such as China and Korea with a high sporadic prevalence of that disease). Similarly, the age-incidence and spectrum of cancers in Lynch syndrome vary significantly based upon the mismatch repair (MMR) gene mutated; this will be described in more detail after the genetics of the syndrome is presented.


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Literature review current through: Oct 2014. | This topic last updated: Nov 5, 2013.
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