Li-Fraumeni syndrome

Li-Fraumeni syndrome (LFS) is a rare hereditary condition. Because of a change in the DNA, children and adults with LFS have a much higher risk of developing cancer. The syndrome has no other symptoms and can only be diagnosed through DNA testing.

What causes LFS?

The (child’s) body consists of billions of cells. Each cell has a nucleus that contains DNA – your genetic code. DNA is made up of thousands of genes, one of which is the TP53 gene. This gene helps the body clear away abnormal cells. In people with LFS, the TP53 gene does not function properly, leaving the body less protected against developing cancer.

Read more: What is childhood cancer?

LFS and cancer

In children with LFS, the most common cancers are brain tumors, sarcomas (bone and soft tissue tumors), adrenocortical carcinoma, and leukemia. In adults, the risk of developing cancers such as breast cancer also increases significantly. Over a lifetime, the overall risk of developing cancer for someone with LFS is 80–90%. People with LFS may also develop cancer more than once.

When do we suspect LFS?

We consider LFS in a child when:

LFS occurs in the family;
the child develops a cancer type typical for LFS;
a change in the tumor tissue is found that is known to be caused by LFS;
a genetic test incidentally finds a change in the DNA that causes LFS.

Monitoring and screening

By monitoring children with LFS regularly (screening), we hope to detect cancer at an early stage. Screening is done according to a European program, in which a child visits the Máxima twice a year.

Physical examination and abdominal ultrasound twice a year
Whole-body MRI once a year*
Brain MRI once a year*

We also advise parents to contact us if their child develops any symptoms between visits.

*Only children with specific changes in the TP53 gene receive MRI scans.

Adults with LFS are monitored at the Antoni van Leeuwenhoek hospital in Amsterdam.

Treatment of cancer

When a child with LFS develops cancer, treatment follows the same protocols as for children without LFS. Surgery is preferred whenever possible, since chemotherapy and radiotherapy can increase the risk of developing another cancer later on. However, chemotherapy and/or radiotherapy are often necessary to achieve a cure.

Inheritance

Both men and women can inherit and pass on the TP53 gene change. Each child of a parent with this genetic change has a 50% chance of inheriting it.

Changes in the TP53 gene can also occur in the egg cell, sperm cell, or shortly after fertilisation. In such cases, the condition is not inherited from either parent. The person is then usually the first in the family with LFS.

Testing options before or during pregnancy

Parents with LFS may be eligible for genetic testing before or during a (future) pregnancy. Testing before pregnancy is called preimplantation genetic diagnosis (PGD). Testing during pregnancy is called prenatal diagnosis (PND).