Rare Hematology News

Disease Profile

Li-Fraumeni 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

All ages

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ICD-10

C97

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)

Sarcoma family syndrome of Li and Fraumeni; SBLA syndrome (Sarcoma, Breast, Leukemia, and Adrenal Gland); LFS1;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Hereditary Cancer Syndromes;

Summary

Li-Fraumeni syndrome (LFS) is an inherited condition that is characterized by an increased risk for certain types of cancer. Affected people often develop cancer at an earlier age than expected and may be diagnosed with more than one cancer during their lifetime. LFS is primarily associated with sarcomas (cancers of muscle, bone or connective tissue), breast cancer, brain tumors, leukemia and adrenocortical carcinoma; however, many other types of cancer have been reported in people with this condition.[1][2] It is caused by changes (mutations) in the TP53 gene and is inherited in an autosomal dominant manner.[1] Management may include high-risk cancer screening and/or prophylactic surgeries.[1][3]

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
30%-79% of people have these symptoms
Breast carcinoma
Breast cancer
0003002
5%-29% of people have these symptoms
Adrenocortical carcinoma
0006744
Astrocytoma
0009592
Central primitive neuroectodermal tumor
0030070
Choroid plexus carcinoma
0030392
Colorectal polyposis
0200063
Ependymoma
0002888
Glioblastoma multiforme
0012174
Osteosarcoma
Bone cell cancer
0002669
Rhabdomyosarcoma
0002859
Stomach cancer
0012126
1%-4% of people have these symptoms
Acute lymphoblastic leukemia
0006721
Acute myeloid leukemia
0004808
Choriocarcinoma
0100768
Colon cancer
0003003
Hodgkin lymphoma
0012189
Medulloblastoma
0002885
Melanoma
0002861
Myelodysplasia
0002863
Neoplasm of head and neck
Head and neck tumor
0012288
Neoplasm of the larynx
0100605
Neoplasm of the lung
Lung tumor
0100526
Neoplasm of the pancreas
Cancer of the pancreas
Pancreatic tumor

[ more ]

0002894
Non-Hodgkin lymphoma
0012539
Ovarian neoplasm
Ovarian tumor
0100615
Prostate cancer
0012125
Renal neoplasm
Renal tumors
0009726
Testicular neoplasm
Testicular tumor
0010788
Thyroid carcinoma
0002890
Percent of people who have these symptoms is not available through HPO
Acute leukemia
0002488
Autosomal dominant inheritance
0000006
Lung adenocarcinoma
0030078
Nephroblastoma
0002667
Soft tissue sarcoma
0030448

Cause

Approximately 80% of families with the features of Li-Fraumeni Syndrome (LFS) have an identifiable change (mutation) in the TP53 gene.[1] TP53 is a tumor suppressor gene, which means that it encodes a protein that stops cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in TP53 result in a defective protein that is unable to carry out its normal role. This contributes to the development of the many different types of tumors found in LFS.[4]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    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

        • MedlinePlus Genetics contains information on Li-Fraumeni 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.

          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) is a catalog of human genes and genetic disorders. Each entry has 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 Li-Fraumeni syndrome. Click on the link to view a sample search on this topic.

            References

            1. Katherine Schneider, MPH, Kristin Zelley, MS, Kim E Nichols, MD, and Judy Garber, MD, MPH. Li-Fraumeni Syndrome. GeneReviews. April 2013; https://www.ncbi.nlm.nih.gov/books/NBK1311/.
            2. Katharine E Brock, MD. Li-Fraumeni Syndrome. Medscape Reference. October 2013; https://emedicine.medscape.com/article/987356-overview.
            3. Genetic Familial High-Risk Assessment: Colorectal Panel Members. Genetic Familial High-Risk Assessment: Colorectal. NCCN Clinical Practice Guidelines in Oncology. February 2014; https://www.nccn.org/about/news/ebulletin/ebulletindetail.aspx?ebulletinid=294.
            4. Li-Fraumeni syndrome. Genetics Home Reference. January 2007; https://www.ghr.nlm.nih.gov/condition/li-fraumeni-syndrome. Accessed 8/8/2012.

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