Lynch syndrome
Last update: October 2025
Lynch syndrome (ORPHA:144; OMIM:120435, 609310, 613244, 614337, 614350; MONDO:0005835) is an inherited disorder that increases the risk of cancer, most importantly the risk of large bowel cancer (colorectal cancer, CRC) and of the lining of the uterus (endometrial cancer). To a lesser extent, individuals with Lynch syndrome are at increased risk of other types of cancer, such as cancer of the ovaries or cancer of the stomach. Characteristics of Lynch syndrome include a relatively young age at diagnosis of the cancer (e.g. mean age at diagnosis is before fifty years of age), multiple tumours in one individual and familial occurrence of colorectal and/or endometrial cancer, most typically in multiple generations. Although people who are diagnosed with Lynch syndrome are at increased risk of cancer, not all of them will develop cancer. In fact, in families with MSH6- and PMS2-associated Lynch syndrome, there might only be few affected family members. The risk of cancer varies with the specific gene involved.
Lynch syndrome is the most common form of inherited colorectal and endometrial cancer. Out of every 100 individuals with colorectal or endometrial cancer, 3 to 5 may have Lynch syndrome. Developing large numbers of colonic polyps is not a feature of Lynch syndrome. In the past, Lynch syndrome was therefore called Hereditary Non-Polyposis Colorectal Cancer (HNPCC) to discriminate it from the inherited forms of colorectal cancer with multiple colonic polyps (i.e. polyposis). In Lynch syndrome generally only few adenomatous polyps, but occasionally more, occur. In view of the other cancer risks in Lynch syndrome, the term HNPCC is no longer used.
Lynch syndrome is an inherited disorder, caused by a pathogenic variant in one of the following four so called DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Also, specific aberrations in the EPCAM gene (located next to MSH2) lead to Lynch syndrome due to subsequent inactivation of MSH2. Very rarely, germline methylation of MLH1-promotor (that initiates the transcription of the MLH1-gene) can cause Lynch syndrome. DNA mismatch repair plays an important role in the repair of errors in the building blocks of DNA that can occur when new cells are formed. Pathogenic variants in any of these genes increase the risk of DNA errors in newly formed cells, which may eventually lead to uncontrolled cell growth and cancer.
Lynch syndrome is inherited in an autosomal dominant way, which means that each child of an individual with Lynch syndrome has a 50% risk of inheriting the pathogenic variant. Both men and women can pass the pathogenic variant on and inherit it. Please note that by inheriting the pathogenic variant, an increased risk of cancer is inherited, not the disease itself. Not all individuals who inherit a pathogenic variant causing Lynch syndrome will eventually develop cancer.
Individuals with Lynch syndrome are advised to have their colon (large bowel) checked regularly by colonoscopy. In addition, women with Lynch syndrome may benefit from regular gynaecological check-ups. For some individuals, preventive surgery of the uterus and ovaries may be an option. When colorectal cancer is diagnosed in an individual with Lynch syndrome, the optimal treatment may differ from individuals without Lynch syndrome. In particular, the choice of surgery or chemotherapy or the use of specific drugs may be different for individuals with Lynch syndrome. Therefore, individuals with Lynch syndrome are recommended to seek expert advice for their screening and, if necessary, treatment.
GeneReviews® - Lynch syndrome
Orphanet: Lynch syndrome
OMIM Lynch syndrome: OMIM:120435 (MSH2), OMIM:609310 (MLH1), OMIM:613244 (EPCAM), OMIM:614337 (PMS2), OMIM:614350 (MSH6)
ClinGen: Lynch syndrome
The Dutch Lynch Polyposis foundation has developed an infographic to inform low literacy patients with Lynch syndrome about the most important aspects of their disorders in the following languages: English, Dutch, Italian, and French.
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Endorsed by ERN GENTURIS* |
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Endorsed guidelines for Lynch and polyposis, and hereditary CRC |
* ERN GENTURIS uses AGREE II as a tool for the endorsement of guidelines. The quality of the guideline is evaluated through assessing the rigor and transparency of the guideline development process. The content of the guideline is not evaluated, although selection of the guideline for endorsement includes expert opinion on the usefulness of the content of the guideline.
ERN GENTURIS webinars - Thematic group 2: Lynch and polyposis
Pre-InSiGHT meeting for patients 2024
A list of healthcare providers with expertise in Thematic Group 2: Lynch syndrome and polyposis can be found here.
A non-exhaustive list of patient associations for genetic tumour risk syndromes in EU member states can be found here.