New series: Rare Diseases - Li-Fraumeni syndrome

In the first of our new series on rare diseases, Dr Raj Thakkar introduces Li-Fraumeni syndrome.

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.

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