Li-Fraumeni syndrome


Li-Fraumeni syndrome (LFS) is a rare inherited condition that predisposes to a wide range of childhood and adult cancers, particularly sarcomas (cancers that affect the connective tissue e.g. muscle and bone) and cancers of the brain, breast and the adrenal gland.


Medical text written November 2013 by Dr Helen Hanson, Consultant in Cancer Genetics, Royal Marsden Hospital NHS Foundation Trust, Sutton, UK.

What are the symptoms?

Symptoms result from the cancers that develop in individuals with LFS. Different members of the same family may develop different cancers and therefore may have varying symptoms due to the wide range of cancers that can occur.

What are the causes?

In the majority of families who have been diagnosed with LFS, a mutation can be identified in a gene called TP53. When working correctly, TP53 prevents cells from developing into cancer cells; however, if there is a mutation in TP53, division and growth of cells is uncontrolled and cancers develop.

How is it diagnosed?

The diagnosis of LFS is made based on clinical criteria. A cancer geneticist will review the family history of cancer and make a diagnosis of LFS if:

  • a sarcoma is found in a person under 45 years of age, and
  • this person has a first-degree relative (mother, father, son, daughter, brother or sister) diagnosed with any cancer when younger than 45 years, and
  • another first- or second-degree relative (aunt, uncle, grandmother, grandfather, granddaughter or grandson) of the person is diagnosed with any cancer when younger than 45 years or a sarcoma at any age.

Li-Fraumeni Like syndrome (LFL) describes families who share some, but not all of the features listed for LFS. A number of definitions exist to make a diagnosis of LFL, but generally families have an individual with a sarcoma at any age or cancer diagnosed in childhood and at least one other family member diagnosed with a specific LFS associated cancer. Mutations in TP53 are less frequently identified in LFL families.

Mutations in TP53 can also be identified in individuals or families who do not fulfil LFS criteria. At present these individuals are treated the same as an LFS family, but cancer risk in these families may differ from classic LFS families.

How is it treated?

Individuals with a TP53 mutation are linked with a specific oncologist or cancer geneticist and offered annual review and/or ‘fast-track’ service for assessment of worrying symptoms.

Treatment of cancers in LFS is determined by the type of cancer involved and may include surgery, chemotherapy or radiotherapy.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
LFS is an autosomal dominant condition. If a TP53 mutation has been identified in an individual, other family members can be tested to see if they have inherited the mutation. Children of an individual with a TP53 mutation have a 50 per cent chance of inheriting the mutation.

Prenatal diagnosis
If a TP53 mutation has been identified as the cause of LFS in a family, prenatal diagnosis is possible. A baby can be tested during pregnancy by chorionic villus sampling or amniocentesis. Pre-implantation genetic diagnosis is also available but both these options require careful genetic counselling.

Is there support?

George Pantziarka TP53 Trust


The George Pantziarka TP53 Trust was established in 2012 to provide support to families affected by Li Fraumeni syndrome and encourage research. It runs a website and forum to bring together all those affected by or interested in the condition and provides access to expert medical information. The Trust intends to gain charitable status and to expand the range of activities they undertake.

Group details last updated February 2013.

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