title: Prenatal diagnosis in Li-Fraumeni syndrome.
abstract: OBJECTIVE
  The hallmark of Li-Fraumeni syndrome (LFS), a familial cancer syndrome, is constitutional TP53 mutation. The authors addressed the complex question of predictive prenatal genetic testing for cancer risk associated with inheritance of TP53 mutation.
  
  
  METHODS
  A classic LFS family including the proband (a 20-month-old boy with rhabdomyosarcoma), his 36-year-old father with osteosarcoma, and his 40-year-old paternal aunt with bilateral breast cancer were identified as carriers of a TP53 germline mutation, a novel 1 base pair deletion in exon 5. A few years later, the mother became pregnant twice, and the parents requested prenatal diagnosis on each occasion. Genetic counseling, psychological evaluation, and support were provided by a multidisciplinary team including a pediatric oncologist, a geneticist, a psychosocial worker, a prenatal care provider, and an ethical representative. After providing overall information on LFS, including the high risk of developing secondary multiple neoplasms in LFS survivors, the committee approved prenatal diagnosis at the request of the family.
  
  
  RESULTS
  In the two pregnancies, the two fetuses were found to be carriers of the same mutation. Nine years from diagnosis of the first tumor, the proband, and a month later his father, developed second tumors, multifocal osteosarcoma and leiomyosarcoma, respectively.
  
  
  CONCLUSIONS
  Children with primary tumors belonging to LFS should be considered for screening for germline mutations and genetic counseling by a multidisciplinary team. Whether family members are found to be positive or negative as carriers, such measures may provide, by reducing uncertainty, psychological benefit to high-risk families.
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel. savigad@post.tau.ac.il
authors.forename: Smadar
authors.initials: S
authors.lastname: Avigad
authors.forename: Dan
authors.initials: D
authors.lastname: Peleg
authors.forename: Dalit
authors.initials: D
authors.lastname: Barel
authors.forename: Hadar
authors.initials: H
authors.lastname: Benyaminy
authors.forename: Noa
authors.initials: N
authors.lastname: Ben-Baruch
authors.forename: Ellen
authors.initials: E
authors.lastname: Taub
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
authors.forename: Yacov
authors.initials: Y
authors.lastname: Goshen
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Cohen
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
authors.forename: Rina
authors.initials: R
authors.lastname: Zaizov
mesh_terms: D000328:Adult; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012208:Rhabdomyosarcoma / Q000235:genetics