Li–Fraumeni syndrome

Li–Fraumeni syndrome
Classification and external resources
ICD-9-CM	758.3
OMIM	151623
DiseasesDB	7450
eMedicine	ped/1305
MeSH	D016864
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Li–Fraumeni syndrome is a rare, autosomal dominant, hereditary disorder {except for the greater than 300,000 Brazilian carriers of the R337H variant that pre-disposes carriers to cancer development. It was named after two American physicians, Frederick Pei Li and Joseph F. Fraumeni, Jr., who first recognized the syndrome after reviewing the medical records and death certificates of 648 childhood rhabdomyosarcoma patients. This syndrome is also known as the sarcoma, breast, leukaemia and adrenal gland (SBLA) syndrome.

The syndrome is linked to germline mutations of the p53 tumor suppressor gene, which encodes a transcription factor (p53) that normally regulates the cell cycle and prevents genomic mutations. The mutations can be inherited, or can arise from de novo mutations early in embryogenesis, or in one of the parent's germ cells.

Li–Fraumeni syndrome is characterized by early onset of cancer, a wide variety of types of cancers, and development of multiple cancers throughout one's life.

Li–Fraumeni syndrome (LFS) is relatively rare; as of 2011, cases had been reported in more than 500 families. The syndrome was discovered using an epidemiological approach. Li and Fraumeni identified four families in which siblings or cousins of rhabdomyosarcoma patients had a childhood sarcoma, which suggested a familial cancer syndrome. Identification of TP53 as the gene affected by mutation was suggested by the same approach. Over half of the cancers in Li-Fraumeni families had been previously associated with inactivating mutations of the p53 gene, and, in one primary research study, DNA sequencing in samples taken from five Li–Fraumeni syndrome families showed autosomal dominant inheritance of a mutated TP53 gene.

LFS1: Mutations in TP53

LFS2: Mutations in CHEK2

Another variant of Li–Fraumeni that remains somewhat controversial, is a mutation of the CHEK2 (or CHK2) gene. CHK2 is also a tumor suppressor gene. CHK2 regulates the action of p53. CHK2 is activated by ATM which detects DNA damage, and in this way DNA damage information can be conveyed to p53 to indirectly arrest the cell cycle at that point for DNA repair to be able to take place or to cause apoptosis (programmed cell death).

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