Li-Fraumeni Syndrome
Li-Fraumeni syndrome, also known as Heritable TP53-related cancer (hTP53rc) syndrome, is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults. A birth prevalence of 1:5.000 has been estimated. The diagnosis should be considered in four different clinical situations:
LFS results from the alteration of one the two parental copies of the TP53 gene encoding the p53 protein. This protein normally acts as a guardian of the genome when DNA damages occur. In patients with an alteration of the gene, the quantity of the normal protein is insufficient, and when DNA damages occur in a cell, they are not corrected and their accumulation leads to the cancerous transformation of the cell.
LFS is a so-called autosomal dominant syndrome: if you inherit the altered copy from only one parent, you can get the disease. In most of the families, the mutation is inherited from the mother or the father, but new alterations occurring in sperm or eggs can end up in every cell of the child and represent at least 14% of the cases.
The risk for a mutation carrier to develop cancer is quite diverse, even within the same family, indicating that some adult mutation carriers do not develop cancer. The risk depends on the type of the mutation and probably on the presence of other genetic variations which act as modifier factors.
Radiotherapy and genotoxic chemotherapies contribute to the development of secondary tumours. Therefore radiotherapy should be avoided and surgical treatment prioritized, but only if this is possible and does not compromise the treatment of cancer.
According to the Guidelines for the Li-Fraumeni and Heritable TP53-related cancer syndromes - Guidelines for the identification of individuals who should be tested for germline disease-causing TP53 variants and for their subsequent clinical management written by ERN GENTURIS:
The surveillance protocols are based, from the first year of life, on abdominal ultrasound every 6 months, annual whole body MRI, annual brain MRI, and in women from 20 years on annual breast MRI. The benefits of such heavy protocols should be carefully analysed and discussed in each family.
Written by ERN GENTURIS
LFS/hTP53rc guideline (genturis.eu) - Guidelines for the Li-Fraumeni and Heritable TP53-related cancer syndromes
Care pathway - Li-Fraumeni and heritable TP53-related cancer (hTP53rc)
Patient journey - Li Fraumeni syndrome