Genetically transmitted cancer predisposition syndrome
associated with soft tissue sarcoma, breast cancer, leukemia, osteosarcoma,
melanoma, and cancer of the colon, pancreas, adrenal cortex, and brain.
Sarcoma, Breast Syndrome, Leukemia, and Adrenal Gland (SBLA)
Syndrome; Sarcoma Family Syndrome.
Li-Fraumeni syndrome is defined by the association of a
proband with a sarcoma who is diagnosed before the proband, i.e., the affected person
who ascertains independently of his relatives in a genetic study,
is age 45 years,
a first-degree relative with any cancer who is younger than 45 years, and a
first- or second-degree relative with any cancer who is younger than 45
years or who has a sarcoma at any age.
Fewer than 400 families reported worldwide.
Autosomal dominant. More than 50% of LFS
patients have an identifiable disease-causing mutation in the TP53 gene (gene
map locus is 17p13.1), 95% of which can be detected by direct
sequence-based DNA testing (clinically available). The CHEK2 gene is also known to be
associated in a few families with LFS, but CHEK2 testing is only available on a
The TP53 gene encodes a cellular tumor antigen protein
(the “guardian of the genome”) that complexes to the large T antigen of
SV40. This protein determines whether cells undergo arrest for purposes of
DNA repair or programmed cell death (apoptosis). In case of damaged DNA, the
normal cellular tumor antigen p53 protein either (1) transcriptionally
activates downstream genes to repair the DNA or (2) directly signals a
“sensor” molecule that proceeds with apoptosis. Mutant cellular tumor
antigen p53 is able to cooperate with RAS oncogene products and blocks normal
cellular tumor antigen p53 protein from appropriately binding, thus favoring
the development or maturation of many tumor types.
Molecular genetics (direct sequence-based DNA
Li-Fraumeni syndrome is a highly penetrant cancer
syndrome. Original descriptions of LFS consisted of autosomal dominant
patterns of osteosarcomas, soft tissue sarcomas, premenopausal breast
cancer, brain tumors, adrenal cortical tumors, and acute leukemias. Since
then, reports of LFS families suggest excess rates of melanoma; cancer of
the stomach, colon, pancreas, and esophagus; and gonadal germ cell tumors
diagnosed at early ages. At-risk children should undergo examination on an
annual basis: complete physical examination, blood cell count, urinalysis,
abdominal ultrasonography examination, and organ-targeted surveillance based
on family history.
No specific precautions to be taken
before anesthesia. However, a thorough evaluation of possible complications
associated with the type of malignancy diagnosed must be done. Proper
laboratory investigations for coagulation disorders, anemia, and
electrolyte imbalances must be performed prior to surgery and anesthesia.
Anesthetic considerations are those
indicated by the pathology involved.
No specific pharmacological
implications other than those associated with the pathology involved and the
treatment performed preoperatively.
Birch JM, Alston RD, McNally RJ, et al: Relative frequency and morphology
of cancers in carriers of germline TP53 mutations. ...