Li-Fraumeni Syndrome (LFS) | Also known as the sarcoma, breast, leukaemia and adrenal gland (SBLA) syndrome

Li-Fraumeni Syndrome (LFS) | Also known as the sarcoma, breast, leukaemia and adrenal gland (SBLA) syndrome

Li-Fraumeni Syndrome (LFS)

Hereditary disorder linked to an increased risk of certain types of cancer, including breast cancer, brain tumors, acute leukemia, soft tissue sarcoma, osteosarcoma and adrenocortical carcinoma. People with Li-Fraumeni syndrome tend to have multiple cancers before the age of 45.

The disease is very rare; it is named after Frederick P. Li and Joseph F. Fraumeni, who first described it.

LFS was first recognized in 1969 by Frederick Li, MD, and Dr. Joseph Fraumeni, Jr., MD, in a study of pediatric and familial cancers (cancers that occur within families) at the National Cancer Institute.


The syndrome is often caused by a germline mutation of a tumor suppressor , the TP53 gene coding for the p53 protein ( chromosome 17 gene locus p13. 1).

The risk of developing cancer at the age of 30 is 50% and is therefore significantly higher than that of the general population (1%).

Tumors associated with Li-Fraumeni syndrome are soft tissue sarcomas, breast cancer , bone sarcomas, leukemia, astrocytomas, plexus carcinomas and carcinomas of the adrenal cortex. An increased incidence of lung cancer , tumors of the stomach and intestines, ovarian cancer and lymphoma was also observed in affected families.

Since no mutation in the TP53 gene can be found in around 30% of those affected, defects in the p53 signal transduction pathway that have not yet been discovered are discussed as further triggers. Diseases associated with mutations in the CHEK2 gene have been referred to as Li-Fraumeni syndrome 2. Another locus was recently identified on chromosome 1 (is one of 23 chromosomes pairs of people . A normal person has two largely identical copies of this chromosome in most of his cells . It is the largest human chromosome).

The most common cancers associated with LFS are:
  • Soft tissue sarcoma
  • Osteosarcoma
  • Brain and central nervous system (CNS) tumors
  • Adrenal cortical carcinoma
  • Acute leukemia
  • Breast cancer
Less often, people with Li-Fraumeni syndrome develop other types of cancer including:
  • Melanoma
  • Thyroid cancer
  • Pulmonary adenocarcinoma
  • Digestive cancer (esophagus, stomach, pancreas or colon)
  • Urologic cancer (kidney, bladder)
  • Cancer of the reproductive system (uterus, ovaries, prostate, gonads)

What is the risk of cancer for people with Li-Fraumeni syndrome?

Due to the many types of cancer that can affect children with Li-Fraumeni syndrome, it is difficult to predict which types of cancer will develop. It is also difficult to know when these cancers will appear.

By the age of 30, it is estimated that half (50%) of all people with Li-Fraumeni syndrome will develop some type of cancer.
By the age of 60, the risk of developing cancer for people with Li-Fraumeni syndrome increases to about 80% –90%.
People with Li-Fraumeni syndrome are more likely to develop multiple cancers.

What is the cause of Li-Fraumeni syndrome?

Li-Fraumeni syndrome is most often caused by changes in the gene called TP53. About 70% of families with LFS will have a mutation in the TP53 gene. The mutation prevents the gene from working properly. One of the main functions of the TP53 gene is to prevent cancer formation.

Not all people with a mutation in the TP53 gene will develop cancer. But the risks are significantly higher for these people than for the general population.

Normally, cells carry 2 working copies of the TP53 gene. One is inherited from the mother and the other from the father. The cells of people with Li-Fraumeni syndrome carry one working copy TP53 and one modified or mutated copy.

When the remaining TP53 working copy is damaged within a cell, it can lead to cancer.

For most children with LFS, the syndrome is inherited from a parent who also has the condition. However, some children with LFS may have a new TP53 mutation (de novo) that is not passed on from a parent. In these cases, the TP53 mutation has occurred in an egg or sperm that formed the child or in one of the child’s cells during the pregnancy. These children are the first in their family to have LFS.

What are the general criteria for a diagnosis of LFS?

Since only about 70% of patients have a detectable mutation of the TP53 gene, the diagnosis is made on the basis of the clinical presentation. The following criteria must be met in order to diagnose Li Fraumeni syndrome:

  • Patient with sarcoma before age 45 plus
  • At least one first-degree relative developed cancer before the age of 45 or developed sarcoma in the course of his life
  • Besides the Li-Fraumeni syndrome in the strict sense, a Li-Fraumeni-like syndrome (is Li-Fraumeni-like syndrome) have been defined, but in which a TP53 mutation is much less frequently detected.

This is clinically defined as follows:

  • Patient with a child tumor, sarcoma, brain tumor or adrenal tumor before the age of 45 plus
  • A first- or second-degree relative developed a tumor associated with Li-Fraumeni syndrome at any age plus
  • Another first or second degree relative developed some tumor before he was 60 years old.

Li Fraumeni syndrome 2 is diagnosed using the following criteria:

  • three independent primary tumors in one person, one before the age of 45
  • a childhood tumor
  • a tumor of the Li Fraumeni tumor spectrum before the age of 45
  • a first- or second-degree relative with a tumor from the LF tumor spectrum and another relative with any tumor disease before the age of 60

How is Li-Fraumeni syndrome diagnosed?

Li-Fraumeni syndrome can be suspected after looking at a person’s or their family’s medical history. To find out the history, a doctor or genetic counselor will ask questions about a person’s health and the health of other family members.

The genetic counselor or doctor will note which family members have developed cancers, as well as the types of cancers and the ages at which these cancers started. From this information, the counselor or doctor builds a family tree and examines it to determine if:

  • There are more cancers than normal.
  • Cancers started at younger ages than expected.
  • Types of cancers are associated with Li-Fraumeni syndrome.

If LFS is suspected, patients may decide to have their blood drawn for analysis. Testing is always optional. DNA will be isolated from cells. The TP53 gene will be checked for any abnormalities (also called mutations). If a TP53 mutation is found, a genetic counselor will work with the family to determine if other members should consider getting tested.

Can Li-Fraumeni syndrome be treated?

Currently, there is no way to correct the TP53 mutation associated with LFS. Cancers resulting from the syndrome can usually be treated. It is normally recommended to avoid radiation therapy if possible.

Are there things people with Li-Fraumeni syndrome can do to prevent cancer?

People with Li-Fraumeni syndrome are encouraged to adopt a healthy lifestyle and have regular physical exams and screening tests.

A healthy lifestyle means in particular:

  • Eat a healthy diet rich in fruits and vegetables
  • Have regular physical activity
  • Limit sun exposure and always use sunscreen and wear protective clothing (long sleeves, hat) when exposed to the sun
  • Avoid unnecessary exposure to radiation
  • Avoid smoking or using products containing tobacco
  • Avoid passive smoking
  • Avoid excessive alcohol consumption


People with Li-Fraumeni syndrome should also watch carefully for signs and symptoms that may indicate cancer and report them promptly to their doctor. These signs and symptoms include:

  • Unexplained weight loss
  • Loss of appetite
  • Unexplained aches, pains, lumps or swelling
  • Headache or changes in vision or nerve function that persist
  • New moles or change in appearance of existing moles
  • Parents of children with Li-Fraumeni syndrome should watch for signs and symptoms of the disease and see a doctor if anything unusual occurs.

People who suspect LFS are advised to inform their healthcare provider. Because LFS is rare, some providers may not be aware of it.

List of all Cancers

The word “cancer” is a generic term for a large group of diseases that can affect any part of the body. We also speak of malignant tumors or neoplasms. One of the hallmarks of cancer is the rapid multiplication of abnormal growing cells, which can invade nearby parts of the body and then migrate to other organs. This is called metastasis, which is the main cause of death from cancer. Types of cancer (in alphabetical order of the area concerned):

Types of Cancer | List all of Cancers | Adult, Children, Head and neck, Digestive and Types of Blood Cancer

Information: Cleverly Smart is not a substitute for a doctor. Always consult a doctor to treat your health condition.

Sources: PinterPandai, Rare Diseases, American Society of Clinical Oncology (ASCO), MedlinePlus

Photo source: NIH Image Gallery / Flickr

Photo explanation: in a new study from the National Cancer Institute (NCI), part of the National Institutes of Health, researchers found a higher-than-expected prevalence of cancer at initial screening in individuals with Li-Fraumeni syndrome (LFS), a rare inherited disorder. which leads to a higher risk of developing certain cancers. This study demonstrates the feasibility of a new, comprehensive cancer screening protocol for this high-risk population.

This image is part of a representative image of a full-body MRI of an LFS patient. Arrows indicate a lesion found to be a lung adenocarcinoma.

Photo credit: National Cancer Institute, NIH

Learn More →

Leave a Reply

Your email address will not be published. Required fields are marked *