What is Li-Fraumeni syndrome?
Li-Fraumeni syndrome (LFS) is a genetic condition that predisposes to the development of malignant tumors. Already in childhood or young adulthood the cancer risk is significantly increased and soft tissue and bone tumors, blood cancer, brain tumors, tumors of the adrenal gland and breast cancer in young women can occur. The LFS is one of the most aggressive cancer predisposition diseases. Therefore, it is of utmost importance to monitor and accompany people with LFS medically.
How is Li-Fraumeni syndrome diagnosed?
LFS can be diagnosed clinically on the basis of classical diagnostic criteria. In addition, there are personal and family constellations in which it makes sense to initiate genetic testing for the presence of an LFS. The diagnosis of an LFS is confirmed with such a genetic test and the detection of a TP53 mutation.
Classical Diagnostic Criteria for the LFS
Chompret Criteria
The following criteria should be examined for the presence of an LFS (one of the following points must be fulfilled). A patient has:
What is the risk of cancer?
A typical feature of Li-Fraumeni syndrome is the occurrence of various types of cancer at an unusually young age. The “core” tumors, i.e. the most frequently occurring cancers, are affected:
Due to the large number of different tumors associated with the LFS, it is impossible to predict which tumor will occur.
Other common cancers are
Already in the first year of life 4% of children with LFS develop a tumor, up to the age of 5 it is almost a quarter of all children (22%) and up to the age of 18 over 40% of children and adolescents with LFS have already developed a tumor.
Typical tumors in childhood are
Typical tumors in adulthood are
Approximately half of LFS carriers suffer from cancer up to the age of 30 and half of male LFS carriers up to the age of 45. At the age of 60 the risk increases to 80-90%, at the age of 70 the probability of developing a tumor is almost 100%. In individual cases, however, it is impossible to predict when a tumor will occur. Unfortunately, some patients also develop cancer several times, especially if they were treated for a malignant disease in childhood.
What causes Li-Fraumeni syndrome?
Li-Fraumeni syndrome is caused by a genetic alteration, a mutation, in a gene called TP53. This gene has a key role in controlling cell growth and tumor development. It determines the fate of cells and initiates a repair process or self-destruction for cells carrying damaged DNA and thus false genetic information material. If this important gene is defective, uncontrolled defective cells multiply and cancer develops.
Each person carries 2 copies of the TP53 gene, one copy from the mother and one copy from the father. With the LFS one of the two copies is damaged. If now also the 2nd still healthy copy of the TP53 gene is damaged, tumors develop.
The disease is transmitted via an autosomal dominant inheritance. That means every second child gets sick. About 70% of people with LFS have inherited the disease from their mother or father. In about 5-20% of cases, the mutation is newly spontaneous, which is called de novo.
Today it is assumed that about 1 out of 5000 people carries a mutation in the LFS gene. In some areas of Brazil there are many more people.
Is there a treatment?
The therapy depends on the type of cancer and, at least so far, is basically the same as for patients without LFS. However, there is one exception: In LFS-associated breast cancer, a mastectomy would be preferred to a lumpectomy (breast preserving surgery) to reduce the risk of a second primary breast cancer and to avoid radiotherapy.
Both diagnostic and therapeutic radiation exposure should be avoided where possible as it favours the development of further tumors. However, the primary cure is always superior to the risk reduction for secondary diseases.
Please ask your attending physician if there are any open clinical trials that could be considered for you.
Surveillance Recommendations for the Early Detection of Cancer
Surveillance Recommendations
The aim is the early recognition of developing complications in order to achieve the best possible treatment results. For this purpose, regular medical examinations are recommended according to the following scheme (examination recommendations of the AACR 2016):
Children and Adolescents (birth up to 18 years)
Adults (from 18 years)
The breast MRI and ultrasound examination of the abdominal organs and pelvis should alternate with the annual whole-body MRI (at least one scan every 6 months).
Self-Care and Support
What should I pay special attention to?
People with Li-Fraumeni syndrome should
Please contact your attending physician or every LFS consultation hour and arrange a prompt appointment for new symptoms, new pain and parental uncertainties in the assessment of a clinical change. The threshold for establishing contact should be as low as possible!