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Li-Fraumeni Syndrome - p53

Clinical Features

The Li-Fraumeni syndrome is characterized by the appearance of different neoplastic syndromes within one family with first tumors occurring in children or adolescents. Tumors of the adrenal glands, soft tissue sarcomas, leucemia and CNS tumors are among the most frequent neoplasms in children. In adults, osteosarcoma and breast cancer are found. The diagnosis Li-Fraumeni syndrome is made on clinical grounds.

 

The revised Chompret criteria cover approx. 90% of all p53 mutation families:

  • Patient with a Li-Fraumeni tumour (soft tissue sarcoma, osteosarcoma, CNS tumour, premenopausal mamma carcinoma, suprarenal gland tumour, leucemia, adenocarcinoma of the lung before the age of 46 years
  • And a first degree relative presenting with a Li-Fraumeni tumour (excluding mamma carcinoma, if initial tumour is a mamma carcinoma, too) before the age of 56 years, or multiple primary tumours of the Li-Fraumeni sprectrum regardless of age
  • Or a patient with multiple tumours (one diagnosed before the age of 46 years and two tumours from the Li-Fraumeni spectrum
  • Or a patient presenting with suprarenal gland tumour or a carcinoma of the plexus coroideus regardless of the family anamnesis.

Additional mutation rates in patients presenting with:

  • Soft tissue carcinoma: 6-14%
  • Mamma carcinoma befor the age of 30 years: 0-9%
  • Suprarenal gland carcinoma: 50-97%
  • Carzinoma of the plexus coroideus: > 50%

20-30% of the tumours, which occur in Li-Fraumeni families are not part of the Li-Fraumeni tumour spectrum. The median age of onset for the primary tumour is approx. at the age of 30 years. Approximately half of the carriers display syn- or metachroneous tumour diseases. Due to the limited ability of p53 mutation carriers to repair radiation induced DNA damage, a conventionel radiation therapy is containdicated in Li-Fraumeni syndrome patients.

Genetic Information

The Li-Fraumeni syndrome and LiFraumeni-Like syndrome both are inherited as autosomal dominant condition caused by genetic alterations in the p53 gene on chromosome 17 (17p13.1). Up to age 70, persons with a p53 mutation have a high risk for clinical manifestation of the syndrome. However, exact estimates are difficult due to the rareness of this condition. 75% of the affected individuals have a positive family history, the remaining cases are caused by de novo mutations.

Prevalence

1 : 15 000

 

Diagnostic

 

Indication

Molecular genetic diagnostics should be initiated if the international clinical criteria for Li-Fraumeni syndrome are fulfilled.

Besides molecular genetic classification of the neoplastic syndrome, mutation detection permits predictive molecular genetic testing of the persons at risk in order to identify a possible carrier status.

Method

All exons of the p53 gene and the flanking regions are analyzed DNA sequencing

MLPA for deletion and duplication testing

Sample Requirement

2 -4 ml of EDTA blood

Duration

approx. 4 weeks

OMIM

151623 Li-Fraumeni-syndrome

191170 p53 gene



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