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Lynch Syndrome

Last updated Nov. 3, 2018

Approved by: Krish Tangella MD, MBA, FCAP

Lynch Syndrome is an autosomal dominant disorder caused by DNA mismatch repair defect. It is an inherited syndrome wherein there are increased malignancy of the gastrointestinal tract, particularly in the colon and rectum.


What are the other Names for this Condition? (Also known as/Synonyms)

  • Familial Non-Polyposis Colon Cancer Syndrome
  • Hereditary Non-Polyposis Colorectal Cancer Syndrome
  • HNPCC (Hereditary Non-Polyposis Colorectal Carcinoma Syndrome)

What is Lynch Syndrome? (Definition/Background Information)

  • Lynch Syndrome is an autosomal dominant disorder caused by DNA mismatch repair defect. It is an inherited syndrome wherein there are increased malignancy of the gastrointestinal tract, particularly in the colon and rectum
  • Based upon histology as described by the pathology reports, 3 major types of the microsatellite instability malignancies have been described. They include:
    • Right-sided colon poorly differentiated cancers
    • Right-sided colon mucinous cancers
    • Adenocarcinomas of colon in any colonic location showing intraepithelial lymphocyte (IEL) response
  • In addition to colorectal cancers, individuals with Lynch Syndrome (Hereditary Non-Polyposis Colorectal Carcinoma-HNPCC) have an increased risk of cancers of following sites:
    • Stomach
    • Ovary
    • Endometrium
    • Small intestine in the duodenum and jejunum
    • Liver
    • Gallbladder ducts
    • Upper urinary tract transitional carcinoma of the ureter and renal pelvis
    • Brain glioblastoma
    • Skin
    • Prostate
  • Individuals with Lynch Syndrome have a 80% lifetime risk of developing colon cancer; most of which occur in the right side of colon

In order to identify high-risk individuals for Lynch Syndrome, two Amsterdam criteria are proposed. They are as follows:

  • Amsterdam criteria:
    • Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two
    • Two successive affected generations
    • One or more colon cancers diagnosed under age 50 years
    • Familial adenomatous polyposis (FAP) has been excluded
  • Amsterdam criteria II:
    • Three or more family members with HNPCC-related cancers, one of whom is a first degree relative of the other two
    • Two successive affected generations
    • One or more of the HNPCC-related cancers diagnosed under age 50 years
    • Familial adenomatous polyposis (FAP) has been excluded

Who gets Lynch Syndrome? (Age and Sex Distribution)

  • The average age of diagnosis of colon cancer in patients with Lynch Syndrome is 44 years
  • The syndrome is seen equally in both males and females
  • All races and ethnic groups can be affected

What are the Risk Factors for Lynch Syndrome? (Predisposing Factors)

The risk factors of Lynch Syndrome include:

  • Individuals with DNA mismatch repair defect
  • Mutations in the MLH1, MLH 3, MSH2, MSH6, PSM 1, PMS2, and TGFBR2 genes increase the risk of developing Lynch Syndrome
  • Family history of the syndrome is a important risk factor, since this is genetic condition risk of cancer is passed from generation to generation

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Lynch Syndrome? (Etiology)

  • Lynch Syndrome is inherited in an autosomal dominant pattern with incomplete penetrance. This means that individuals inherit the defective genes from one of the parents. This affected parent may not have a colon cancer
  • Due to incomplete penetrance of the genes, it is difficult to predict who will get colon cancer, even if that individual is positive for the mismatch mutation gene test
  • Mutations in the MLH1, MLH 3, MSH2, MSH6, PSM 1, PMS2, and TGFBR2 genes increase the risk of developing Lynch Syndrome. Of these, MSH2 occurs with 60% frequency, MLH1 with 30% frequency and MSH6 with 7-10% frequency. Others genes namely, MLH 3, PSM 1, PMS2, and TGFBR2 genes occur with rare frequency
  • All of these genes are involved in the repair of mistakes that occur when DNA is copied during a cell division. The cells have a repair mechanism to rectify the errors made during cell division. Mutations affect the repair mechanism resulting in DNA with errors. These errors in DNA can result in cells becoming cancerous
  • It is important to note that presence of DNA mismatch repair genes mutation does not mean that individual has colon cancer. It only indicates the predisposition to develop colon cancers

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly functioning gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Lynch Syndrome?

Majority have no signs and symptoms of Lynch Syndrome, until colon cancer develops. When an individual develops colon cancer, the signs and symptoms may include:

  • Abdominal mass
  • Abdominal pain
  • Rectal bleeding
  • Anemia
  • Weakness and fatigue
  • Change in bowel habits
  • Diarrhea
  • Unexplained weight loss
  • Loss of appetite

How is Lynch Syndrome Diagnosed?

Lynch Syndrome is diagnosed using the following tools:

  • Evaluation of the individual’s medical history and a through physical examination
  • Family history of colon cancer is often present
  • Complete blood cell (CBC) count
  • Carcinoembryonic antigen testing (for colon cancers), and liver function tests (may be abnormal in metastatic colon cancer to liver)
  • Screening colonoscopy with biopsy can help in determining the histologic type of polyps (adenomatous type as opposed to hyperplastic type of polyps)
  • Fecal occult blood test (FOBT) to detect blood in stool as one would see in colon cancer. Presence of blood in stools does not mean that individual has cancer; blood in stool can be seen due to non-cancer reasons too
  • Double contrast barium enema can determine the presence of any masses as demonstrated by a filling defect during the study
  • Computed tomography (CT) scan of the abdomen and pelvis: A noninvasive test used to diagnose and treat medical conditions, by combining a special x-ray machine with computers, to produce images of the body insides
  • MRI of the abdomen: It helps produce high-quality pictures of certain body parts including the tissues, muscles, nerves, and bones
  • Ultrasound of the abdomen: A procedure where high-frequency sound waves are used to produce real-time images
  • Digital rectal exam
  • Special immunohistochemical analysis (IHC) called MSI (microsatellite assay) can be performed on formalin fixed paraffin embedded tumor blocks by pathologist
  • Follow up genetic test is necessary, if IHC results indicate a possible Lynch Syndrome due to positive microsatellite instability

Note: It is important to note that presence of DNA mismatch repair genes mutation does not mean that individual has colon cancer. It only indicates the predisposition to develop colon cancers

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Lynch Syndrome?

The complications of Lynch Syndrome may include:

  • The polyps can develop into cancers
  • The polyps can bleed and cause anemia
  • Cancers can metastasize

How is Lynch Syndrome Treated?

Since Lynch Syndrome is a genetic disorder, there is no cure for the condition. The efforts to decrease the complication due to the genetic defects by various methods are the treatment of choice. The following methods may be used in the treatment of Lynch Syndrome:

  • If cancer of colon develops then surgery remains the main option. In majority of individuals, surgical resection with clear margins of the tumor results in a cure, especially if it behaves in a benign manner
  • Long-term follow-up is required, because recurrence at the tumor at site of surgery or metastasis in distant sites have been reported many years after surgery even with ‘benign-appearing’ tumors
  • Radiotherapy can be used as primary therapy in situations where the tumor cannot be removed completely, or when the tumor reappears after surgery
  • Radiotherapy can also be used as additional therapy after surgery, if there is a possibility of tumor recurrence after surgery, or if there are inadequate margins (possibility of tumor left behind) following surgery. In some cases due to location of tumor, complete surgical removal is difficult.
  • Chemotherapy can be used for treating the tumors in the following situations:
    • Tumors cannot be removed completely (incomplete surgical resection)
    • Tumors that recur after surgery
    • Tumors that have spread to distant parts of the body
  • Prophylactic removal of the colon prior to the development of cancer is generally not recommended. Screening colonoscopy is an effective measure to prevent colon cancer
  • Treatment of cancers as they develop through surgery, chemotherapy and/ or radiation depending on the clinical situation

How can Lynch Syndrome be Prevented?

There is no definitive prevention of Lynch Syndrome, since it is a genetic disorder:

  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in better understanding the risks during pregnancy
  • If there is a family history of the condition, then genetic counseling may help couples assess risks while planning for a child
  • At risk family members who have not yet been genetically tested should undergo annual colonoscopy
  • Active research is exploring treatment and prevention options for inherited and acquired genetic disorders
  • Annual gynecologic examinations
  • Screening for endometrial biopsy
  • Serum CA 125

Female patients with Lynch Syndrome who have been diagnosed with colorectal cancer may consider prophylactic removal of the uterus and ovaries to prevent the occurrence of endometrial and ovarian cancer (which have known to occur in some cases).

What is the Prognosis of Lynch Syndrome? (Outcomes/Resolutions)

The prognosis of Lynch Syndrome depends upon a set of several factors, which include:

  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • The surgical respectability of the tumor (meaning, if the tumor can be removed completely)
  • Overall health of the individual. Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual. Older individuals generally have poorer prognosis than younger individuals
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment. Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment

An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment.

  • Regular medical checkup can help detect cancers early, which when treated appropriately can increase life expectancy
  • As with any tumor, it is important to have follow-up appointments with a physician to monitor for any returning tumors

Additional and Relevant Useful Information for Lynch Syndrome:

  • Lynch Syndrome is named after Henry T. Lynch, Professor of Medicine, who described the syndrome in 1966
  • A tumor is an abnormal growth of tissue arising due to uncontrolled and rapid multiplication of cells that serve no function. They are also called neoplasms. Tumors can be benign or cancerous. A benign tumor may generally indicate no threat to one’s health; it also means that it is not “cancerous”

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Nov. 29, 2015
Last updated: Nov. 3, 2018