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Li Fraumeni syndrome (LFS) consists of a predisposition to developing any of a wide variety of tumors. It is difficult to estimate the incidence of this rare disease because its definition raises a problem of nosological classification. The disease affects predominantly young persons. The historical and classical definition is based on familial criteria, i.e. the observation of a sarcoma in a patient under 45, who has either a first-degree relative who developed any type of cancer before the age of 45, or a second degree-relative who had a cancer or a sarcoma before the age of 45. The most characteristic tumors are osteosarcomas, soft-tissue sarcomas, breast cancers in young subjects, leukemias/lymphomas, cerebral tumors and adenocarcinoma; however, every type of tumor can be observed. A germinal mutation of the TP53 gene is found in about 70% of the LFS families as well as in some families or patients with disease patterns suggestive of the syndrome without fulfilling strictly the criteria. The risk of developing a cancer, for a patient carrying deleterious mutation of the TP53 gene, is 15% at 15 years, 80% for 50 year old women and 40% for men of the same age; the significant difference between the sexes is almost entirely explained by breast cancers. The risk of developing a second cancer, especially a radiation-induced cancer, is high. The disease is transmitted as an autosomal dominant trait. Genetic counseling is difficult due to the broad spectrum of tumors and their appearance at any age, especially in childhood. No specific surveillance measures, except breast cancer for women after the age of 20, can be effective. |