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Disease Profile

Lynch syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Adult

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ICD-10

D48.9

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Colorectal cancer, hereditary nonpolyposis; Hereditary nonpolyposis colorectal cancer; HNPCC;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Female Reproductive Diseases;

Summary

Lynch syndrome is a genetic disorder that causes an increased risk of developing certain types of cancer such as colon and rectal cancer, as well as cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, and prostate. Women with Lynch syndrome also have a high risk of developing uterine cancer (also called endometrial cancer) and ovarian cancer. Even though the disorder was originally described as not involving noncancerous (benign) growths (polyps) in the colon, people with Lynch syndrome may occasionally have colon polyps. Lynch syndrome has an autosomal dominant pattern of inheritance and is caused by a mutation in the MLH1, MSH2, MSH6, PMS2 or EPCAM gene.[1][2] Treatment of colon cancer is surgical removal of the affected part of the colon (colectomy). People with Lynch syndrome should have routine colonoscopies.[2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Colon cancer
0003003
Constipation
0002019
Fatigue
Tired
Tiredness

[ more ]

0012378
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Glioblastoma multiforme
0012174
Malabsorption
Intestinal malabsorption
0002024
Weight loss
0001824
30%-79% of people have these symptoms
Anxiety
Excessive, persistent worry and fear
0000739
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

0007018
Death in early adulthood
0100613
Death in infancy
Infantile death
Lethal in infancy

[ more ]

0001522
Depressivity
Depression
0000716
Hypertonia
0001276
Increased intracranial pressure
Rise in pressure inside skull
0002516
Irritability
Irritable
0000737
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches

[ more ]

0002076
Muscular hypotonia
Low or weak muscle tone
0001252
Nausea and vomiting
0002017
Neoplasm of the rectum
Rectal tumor
0100743
Seizure
0001250
5%-29% of people have these symptoms
Abnormal pyramidal sign
0007256
Agnosia
0010524
Amaurosis fugax
0100576
Basal cell carcinoma
0002671
Benign neoplasm of the central nervous system
0100835
Cardiac diverticulum
0100571
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Dysarthria
Difficulty articulating speech
0001260
Dysgraphia
0010526
Dyskinesia
Disorder of involuntary muscle movements
0100660
Flexion contracture
Flexed joint that cannot be straightened
0001371
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Hallucinations
Hallucination
Sensory hallucination

[ more ]

0000738
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Hepatocellular carcinoma
0001402
Intestinal polyposis
0200008
Memory impairment
Forgetfulness
Memory loss
Memory problems
Poor memory

[ more ]

0002354
Neoplasm of the skeletal system
Skeletal tumor
0010622
Neoplasm of the thyroid gland
0100031
Neuroblastoma
Cancer of early nerve cells
0003006
Ovarian neoplasm
Ovarian tumor
0100615
Pancreatic adenocarcinoma
0006725
Paresthesia
Pins and needles feeling
Tingling

[ more ]

0003401
Pituitary adenoma
Noncancerous tumor in pituitary gland
0002893
Urinary tract neoplasm
0010786
Visual field defect
Partial loss of field of vision
0001123

Cause

Lynch syndrome is caused by mutations in at least 5 genes (MLH1, MSH2, MSH6, PMS2 or EPCAM). All of these genes are involved in the repair of mistakes made when DNA is copied (DNA replication) in preparation for cell division. Mutations in any of these genes prevent the proper repair of DNA replication mistakes. As the abnormal cells continue to divide, the accumulated mistakes can lead to uncontrolled cell growth and possibly cancer. Although mutations in these genes predispose individuals to cancer, not all people who carry these mutations develop cancerous tumors.[1][2]

Diagnosis

The diagnosis of Lynch syndrome can be made on the basis of the Amsterdam Clinical Criteria or on the basis of molecular genetic testing for germline mutations in one of several mismatch repair (MMR) genes.[2]

To read detailed diagnostic strategies, please visit the following link from GeneReviews: https://www.ncbi.nlm.nih.gov/books/NBK1211/#hnpcc.Diagnosis

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Lynch Syndrome International (LSI) provides Lynch syndrome information For Survivors and For Professionals. Click on For Survivors or For Professionals to visit the LSI Web site and view the information pages.
        • Genetics Home Reference (GHR) contains information on Lynch syndrome. This website is maintained by the National Library of Medicine.
        • The National Cancer Institute provides the most current information on cancer for patients, health professionals, and the general public.
        • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Lynch syndrome in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Lynch syndrome. Click on the link to view a sample search on this topic.

            References

            1. Lynch syndrome. Genetics Home Reference Web site. April 11, 2017; https://ghr.nlm.nih.gov/condition=lynchsyndrome.
            2. Kohlmann W & Gruber S. Lynch syndrome. GeneReviews. May 22, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1211/.

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