What is it?
- Autosomally inherited condition, first described in 1969.
- Li-Fraumeni syndrome is very rare. Data vary but fewer than 500 families are thought to have been affected globally.
- The syndrome confers a predisposition to developing cancer at a young age.
- The p53 mutation is the most prevalent genetic anomaly in Li-Fraumeni syndrome and is seen in 70% of patients. p53, which is found on chromosome 17, normally acts as a tumour suppressor gene.
- CHEK2 gene mutations have also been documented in Li-Fraumeni syndrome.
Who is at risk?
- The condition is inherited in an autosomal dominant fashion, so it is often seen in family clusters; however, genetic mutations can also occur.
What are the symptoms?
- Cancers tend to occur at a young age and commonly include sarcoma, osteosarcoma, premenopausal breast cancer, leukaemia, cerebral tumours and adrenal tumours.
- While virtually any organ may be susceptible to cancers in patients with Li-Fraumeni syndrome, other tumours that have been reported include Wilms' tumour, malignant melanoma, pulmonary, GI and gonadal tumours.
- There are a number of definitions of Li-Fraumeni syndrome in the literature. The classic criteria of Li-Fraumeni syndrome are when the index patient has been diagnosed with sarcoma before the age of 45, in addition to having a first-degree relative affected by any cancer before the age of 45, and the index patient also having a firstor second-degree relative affected by any cancer prior to age 45 or by a sarcoma at any age.
How is it managed?
- Genetic counselling.
- Those with the mutation will need psychological support, education and regular follow-up, given that their risk of developing a malignancy is so high.
- Education should include the symptoms of potential malignancies.
- Half of those affected will develop a tumour by age 40 and 90% by age 60. Affected individuals are also at risk of developing cancers at multiple sites.
- Regular breast self-examination, physical examination by a doctor and annual breast cancer screening are all advised.
- Regular, thorough physical examinations are advocated.
- Colonoscopies every two to five years should be considered.
- The evidence behind what imaging modalities to perform, such as ultrasound, CT, MRI and PET, and how often they should be screened is unclear.
- Individual cancers tend to be managed in the usual way.
- Dr Thakkar is a GP in Wooburn Green, Bucks.
