Li-FraumeniSyndrome: A dopting a Diagnosis with an Unknown Family History
Introduction: Li-Fraumeni Syndrome (LFS) is a rare, autosomal dominant disease that is typically screenedfor and identified in patients with a known history of cancer and family history ofcancer.
Presentation of Case: Ms. DA is an adopted 39-year-old South American female with a past medical history of iron deficiency anemia, celiac disease, and polio. She presented with ductal carcinoma in-situ with spindle cell atypia at age 35 and leiomyosarcoma of the ankle at age 36. Genetic counseling was offered due to her age and cancer types, with subsequent genetic testing revealing a TP53-R337H mutation, which was diagnostic of LFS. Given her high risk status, extensive cancer screenings at common LFS body sites were recommended, but she was lost to follow-up. Four years later, she returned after discovering a new right breast mass on self-examination. She was referred to a new breast surgeon, who was able to establish consistent and close follow-up while providing counseling and education regarding lifetime risk and cancer trajectory of classical LFS compared to the Brazilian LFS-subtype.
Conclusion: The importance of having a high level of suspicion for patients with anunknown family history is crucial as seen in this case. Without a biological familyhistory, clinicians rely on their judgement to decide when further work-up is warranted.Advancements in medicine and genetic testing have increased the ability to accuratelydiagnose genetic diseases to help patients make life-saving decisions about theirhealth.
Li FP, Fraumeni JF, Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med. 1969, 71:747-752
Peng G, Bojadzieva J, Ballinger ML, Li J, Blackford AL, Mai PL, Savage SA, Thomas DM, Strong LC, Wang W. Estimating tp53 mutation carrier probability in families with li-fraumeni syndrome using lfspro. Cancer Epidemiol Biomarkers Prev. 2017, 26:837-844
Malkin D. Li-fraumeni syndrome. Genes Cancer. 2011, 2:475-484
Mai PL, Best AF, Peters JA, DeCastro RM, Khincha PP, Loud JT, Bremer RC, Rosenberg PS, Savage SA. Risks of first and subsequent cancers among tp53 mutation carriers in the national cancer institute li-fraumeni syndrome cohort. Cancer. 2016, 122:3673-3681
Hisada M, Garber JE, Fung CY, Fraumeni JF, Jr., Li FP. Multiple primary cancers in families with li-fraumeni syndrome. J Natl Cancer Inst. 1998, 90:606-611
Schneider K, Zelley K, Nichols KE, Garber J. Li-fraumeni syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, eds. Genereviews((r)). Seattle (WA); 1993.
Li FP, Fraumeni JF, Jr., Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, Miller RW. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988, 48:5358-5362
Chompret A, Abel A, Stoppa-Lyonnet D, Brugieres L, Pages S, Feunteun J, Bonaiti-Pellie C. Sensitivity and predictive value of criteria for p53 germline mutation screening. J Med Genet. 2001, 38:43-47
Birch JM, Hartley AL, Tricker KJ, Prosser J, Condie A, Kelsey AM, Harris M, Jones PH, Binchy A, Crowther D, et al. Prevalence and diversity of constitutional mutations in the p53 gene among 21 li-fraumeni families. Cancer Res. 1994, 54:1298-1304
Eeles RA. Germline mutations in the tp53 gene. Cancer Surv. 1995, 25:101-124
Gonzalez KD, Noltner KA, Buzin CH, Gu D, Wen-Fong CY, Nguyen VQ, Han JH, Lowstuter K, Longmate J, Sommer SS, Weitzel JN. Beyond li fraumeni syndrome: Clinical characteristics of families with p53 germline mutations. J Clin Oncol. 2009, 27:1250-1256
Ruijs MW, Verhoef S, Rookus MA, Pruntel R, van der Hout AH, Hogervorst FB, Kluijt I, Sijmons RH, Aalfs CM, Wagner A, Ausems MG, Hoogerbrugge N, van Asperen CJ, Gomez Garcia EB, Meijers-Heijboer H, Ten Kate LP, Menko FH, van 't Veer LJ. Tp53 germline mutation testing in 180 families suspected of li-fraumeni syndrome: Mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet. 2010, 47:421-428
Win AK, Young JP, Lindor NM, Tucker KM, Ahnen DJ, Young GP, Buchanan DD, Clendenning M, Giles GG, Winship I, Macrae FA, Goldblatt J, Southey MC, Arnold J, Thibodeau SN, Gunawardena SR, Bapat B, Baron JA, Casey G, Gallinger S, Le Marchand L, Newcomb PA, Haile RW, Hopper JL, Jenkins MA. Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: A prospective cohort study. J Clin Oncol. 2012, 30:958-964
Palmero EI, Schuler-Faccini L, Caleffi M, Achatz MI, Olivier M, Martel-Planche G, Marcel V, Aguiar E, Giacomazzi J, Ewald IP, Giugliani R, Hainaut P, Ashton-Prolla P. Detection of r337h, a germline tp53 mutation predisposing to multiple cancers, in asymptomatic women participating in a breast cancer screening program in southern brazil. Cancer Lett. 2008, 261:21-25
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