Types of cancer

Li-Fraumeni Syndrome

Li-Fraumeni syndrome is caused by an alteration in the TP53 gene, whose function is to suppress tumors, and is hereditary. Carriers of the disease have a 50% chance of developing cancer before their 30's and 90% of them have cancer before their 70's. Learn more.
5 min read
per: Grupo Oncoclínicas
Li-Fraumeni Syndrome
Li-Fraumeni syndrome is rare and autosomal dominant, meaning the father or mother can pass it on to their children.

What is Li-Fraumeni Syndrome (LFS)

Li-Fraumeni syndrome is caused by an inherited change in the TP53 gene, which weakens the ability of cells to control various vital systems. The result of this loss of control of critical cell mechanisms increases the likelihood of a cancer diagnosis: Li-Fraumeni syndrome carriers have about a 50% risk of developing cancer before age 30, and 90% of them have cancer before 70 years old. When the syndrome manifests in childhood, patients are more likely to have more than one type of cancer in their lifetime or to have more than one cancer when they experience typical symptoms.

The TP53 gene has the role of suppressing tumors, ensuring that when cells divide – a process that happens all the time in the body – there are no “mistakes” in the process. If DNA is damaged in cell division, normal TP53 has the ability to stop the entire process and send the cell for repair. When the damage is too extensive, the cell enters a state of “replicative senescence”, that is, it can no longer divide or even activate self-destruction mechanisms, as it represents a risk to other cells.

People with Li-Fraumeni syndrome are already born with one copy of this corrupted gene (it can be either the maternal or paternal copy) in every cell in the body and are at an increased risk of developing the disease at any stage of life.

Because these people still have a normal copy of the gene, another event that causes the normal copy to lose its function would have to affect some cell during life for cancer to occur. Therefore, it is not certain that a person with Li-Fraumeni syndrome will have cancer in life, in which organ or at what age: the phenomenon of loss of the normal copy is unpredictable and, in certain carriers, it may never occur.

Cancers associated with Li-Fraumeni syndrome

Li-Fraumeni syndrome is rare and autosomal dominant, meaning the father or mother can pass it on to their children. Each offspring has a 50% risk of carrying the same syndrome, and the presence of a mutated copy of the gene is enough to increase the likelihood of developing cancer.

Cancers associated with Li-Fraumeni syndrome are:

  • Bone and soft tissue sarcomas;
  • Genetic breast cancer;
  • Chest cancer;
  • Brain tumors;
  • Adrenocortical cancer;
  • Genetic leukemia;
  • Lymphoma;
  • Glioblastoma; and
  • Rhabdomyosarcoma.

Li-Fraumeni Syndrome – who should be tested

Since the main sign that a person may have Li-Fraumeni syndrome (LFS) is the development of certain types of cancer, it is important to know who should be tested for the change in the TP53 gene.

LFS may be suspected if someone has a personal or family history of the cancers mentioned above. Patients who belong to families with multiple childhood cancers, family members with multiple cancers, or specific rare cancers such as adrenocortical carcinoma or choroid plexus tumors should report these events to their physicians, inquiring about possible heredity.

If the professional considers that the patient may have the syndrome, a referral will be made to a specialist in genetic counseling. It is he who will explain details about the disease and risks, which vary from family to family. Above all, the genetic counselor will discuss the implications of having a DNA test and the meaning of a positive or negative test. It will be clarified which family member would be the best candidate for the test (it is not necessary to test everyone at first) and even information about reimbursement of the exam before the exam is taken.

If the results are positive (that is, the patient tested has the mutation), the person has a higher lifetime risk of developing cancer and has a 50% chance of passing the variant on to their children.

Diagnosis of Li-Fraumeni Syndrome

The possibility of a mass diagnosis to identify families with the syndrome is a controversial topic due to the risk-benefit ratio not yet very clear – the same goes for early detection in newborns.

In Brazil, researchers from Unicamp developed a kit for the detection of mutations linked to Li-Fraumeni syndrome in newborns. The idea is to incorporate it into the foot test, which identifies more than 30 diseases. There is no consensus on the topic. Genetic mapping in patients with a family history of multiple cancers is advisable.

Li-Fraumeni syndrome is diagnosed based on clinical criteria and confirmed by genetic testing for the mutation in the TP53 gene.

American Society of Clinical Oncology criteria for testing:

  • A sarcoma diagnosed before age 45;
  • A first-degree relative with cancer before age 45; and
  • A first-degree or second-degree relative with any cancer before age 45 or a sarcoma at any age.

Chompret criteria for testing:

Criterion 1 – Tumor belonging to the Li-Fraumeni syndrome spectrum (osteosarcoma, brain tumor, etc.) before age 46 years and at least one first- or second-degree family member with a Li-Fraumeni syndrome-related tumor, except breast cancer if the individual has the disease before age 56 or has multiple tumors;

Criterion 2 – a person with multiple tumors, except multiple breast tumors, two of which belong to the LFS tumor spectrum and the first occurred before age 46; and

Criterion 3 – a family member diagnosed with adrenocortical carcinoma or a tumor in the choroid plexus, a membrane that surrounds the brain, regardless of family history.


There is no standard treatment or cure for LFS. With a few exceptions, cancers in people with LFS are treated in the same way as cancers in other patients. There are some differences, such as special care with the use of exams and treatments that involve radiation.

Radiation/radiotherapy vs Li-Fraumeni syndrome

Research indicates that individuals with LFS appear to have an elevated risk of radiation-induced cancer. Therefore, the use of radiotherapy should be approached with caution. Computed tomography (CT), mammography, and other diagnostic techniques involving ionizing radiation should be limited. Radiation therapy may only be considered in special situations, according to the doctor’s analysis.


As the syndrome predisposes to the development of several types of cancer, carriers must incorporate a healthy lifestyle, with measures that reduce the risk of having the neoplasm. General recommendations are already well known, such as not smoking, controlling weight, using sunscreen etc.

In families in which the diagnosis of FHL has already occurred, adherence to preventive screening is very useful. Some surveillance recommendations are recommended, such as the use of whole-body MRI scans for patients with LFS.

Overall, recommendations for screening in families where the syndrome is present involve:

Children (up to 18 years old)

  • Complete physical examination every 3-4 months;
  • Ultrasound of the abdomen and pelvis every 3-4 and blood tests (adrenocortical carcinoma);
  • Annual brain resonance imaging (MRI) (brain cancer); and
  • Annual full-body MRI (soft tissue and bone sarcoma).


  • Complete physical examination every 6 months;
  • Clinical breast exam twice a year – after age 20, annual breast MRI alternating with full body MRI every 6 months (breast cancer);
  • MRI of the brain, first with contrast and then without contrast if previous MRI normal (brain tumor);
  • Annual full-body MRI, ultrasound of the abdomen and pelvis every 12 months (soft tissue and bone sarcoma);
  • Upper endoscopy and colonoscopy every 2-5 years (gastrointestinal cancer); and
  • Annual skin examination (melanoma).


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