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Li-Fraumeni syndrome(LFS)

MedGen UID:
88399
Concept ID:
C0085390
Disease or Syndrome
Synonyms: LFS; Sarcoma family syndrome of Li and Fraumeni
SNOMED CT: Li-Fraumeni syndrome (428850001)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): TP53 (17p13.1)
Related gene: CHEK2
 
Monarch Initiative: MONDO:0018875
OMIM®: 151623
OMIM® Phenotypic series: PS151623
Orphanet: ORPHA524

Disease characteristics

Excerpted from the GeneReview: Li-Fraumeni Syndrome
Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with high risks for a broad spectrum of cancers including early-onset cancers. Five cancer types account for the majority of LFS tumors: adrenocortical carcinomas, breast cancer, central nervous system tumors, osteosarcomas, and soft-tissue sarcomas. Other cancers associated with LFS include leukemia, colorectal cancer, stomach cancer, lung cancer, melanoma, pediatric head and neck cancers, pancreatic cancer, and prostate cancer. Cancer survivors are at increased risk for developing additional primary cancers and treatment-related secondary cancers. The lifetime risks of cancer for women and men with classic LFS are 90% and 70%, respectively, and 50% of cancers occur prior to age 40 years. [from GeneReviews]
Authors:
Katherine Schneider  |  Kristin Zelley  |  Kim E Nichols, et. al.   view full author information

Additional descriptions

From OMIM
Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous inherited cancer syndrome. LFS is characterized by autosomal dominant inheritance and early onset of tumors, multiple tumors within an individual, and multiple affected family members. In contrast to other inherited cancer syndromes, which are predominantly characterized by site-specific cancers, LFS presents with a variety of tumor types. The most common types are soft tissue sarcomas and osteosarcomas, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma. Classic LFS is defined as a proband with a sarcoma before the age of 45 years and a first-degree relative with any cancer before the age of 45 years and 1 additional first- or second-degree relative in the same lineage with any cancer before the age of 45 years or a sarcoma at any age (Li et al., 1988). Li-Fraumeni-like syndrome (LFL) is defined as a proband with any childhood cancer, or a sarcoma, brain tumor, or adrenocortical tumor before the age of 45 years, plus a first- or second-degree relative in the same lineage with a typical LFS tumor at any age, and an additional first- or second-degree relative in the same lineage with any cancer before the age of 60 years (Birch et al., 1994). A less restrictive definition of LFL is 2 different LFS-related tumors in first- or second-degree relatives at any age (Eeles, 1995). Approximately 70% of LFS cases and 40% of LFL cases contain germline mutations in the p53 gene on chromosome 17p13.1 (Bachinski et al., 2005).  http://www.omim.org/entry/151623
From MedlinePlus Genetics
Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults.

A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different.

The cancers most often associated with Li-Fraumeni syndrome include breast cancer, a form of bone cancer called osteosarcoma, and cancers of soft tissues (such as muscle) called soft tissue sarcomas. Other cancers commonly seen in this syndrome include brain tumors, cancers of blood-forming tissues (leukemias), and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney). Several other types of cancer also occur more frequently in people with Li-Fraumeni syndrome.  https://medlineplus.gov/genetics/condition/li-fraumeni-syndrome

Professional guidelines

PubMed

Daly MB, Pal T, Maxwell KN, Churpek J, Kohlmann W, AlHilli Z, Arun B, Buys SS, Cheng H, Domchek SM, Friedman S, Giri V, Goggins M, Hagemann A, Hendrix A, Hutton ML, Karlan BY, Kassem N, Khan S, Khoury K, Kurian AW, Laronga C, Mak JS, Mansour J, McDonnell K, Menendez CS, Merajver SD, Norquist BS, Offit K, Rash D, Reiser G, Senter-Jamieson L, Shannon KM, Visvanathan K, Welborn J, Wick MJ, Wood M, Yurgelun MB, Dwyer MA, Darlow SD
J Natl Compr Canc Netw 2023 Oct;21(10):1000-1010. doi: 10.6004/jnccn.2023.0051. PMID: 37856201
Rebuzzi F, Ulivi P, Tedaldi G
Int J Mol Sci 2023 Jan 21;24(3) doi: 10.3390/ijms24032137. PMID: 36768460Free PMC Article
Daly MB, Pal T, Berry MP, Buys SS, Dickson P, Domchek SM, Elkhanany A, Friedman S, Goggins M, Hutton ML; CGC, Karlan BY, Khan S, Klein C, Kohlmann W; CGC, Kurian AW, Laronga C, Litton JK, Mak JS; LCGC, Menendez CS, Merajver SD, Norquist BS, Offit K, Pederson HJ, Reiser G; CGC, Senter-Jamieson L; CGC, Shannon KM, Shatsky R, Visvanathan K, Weitzel JN, Wick MJ, Wisinski KB, Yurgelun MB, Darlow SD, Dwyer MA
J Natl Compr Canc Netw 2021 Jan 6;19(1):77-102. doi: 10.6004/jnccn.2021.0001. PMID: 33406487

Curated

UK NICE Clinical Guideline CG164, Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer, 2023

Suggested Reading

Recent clinical studies

Etiology

Batchala PP, Eluvathingal Muttikkal TJ, Mukherjee S
Radiol Clin North Am 2021 May;59(3):471-500. doi: 10.1016/j.rcl.2021.01.009. PMID: 33926690
Raimundo L, Ramos H, Loureiro JB, Calheiros J, Saraiva L
Biochim Biophys Acta Rev Cancer 2020 Jan;1873(1):188339. Epub 2020 Jan 7 doi: 10.1016/j.bbcan.2020.188339. PMID: 31917206
Swaminathan M, Bannon SA, Routbort M, Naqvi K, Kadia TM, Takahashi K, Alvarado Y, Ravandi-Kashani F, Patel KP, Champlin R, Kantarjian H, Strong L, DiNardo CD
Cold Spring Harb Mol Case Stud 2019 Feb;5(1) Epub 2019 Feb 1 doi: 10.1101/mcs.a003210. PMID: 30709875Free PMC Article
Kennedy AL, Shimamura A
Blood 2019 Mar 7;133(10):1071-1085. Epub 2019 Jan 22 doi: 10.1182/blood-2018-10-844662. PMID: 30670445Free PMC Article
Stoffel EM
Gastroenterol Clin North Am 2016 Sep;45(3):509-27. doi: 10.1016/j.gtc.2016.04.008. PMID: 27546846

Diagnosis

Light N, Layeghifard M, Attery A, Subasri V, Zatzman M, Anderson ND, Hatkar R, Blay S, Chen D, Novokmet A, Fuligni F, Tran J, de Borja R, Agarwal H, Waldman L, Abegglen LM, Albertson D, Finlay JL, Hansford JR, Behjati S, Villani A, Gerstung M, Alexandrov LB, Somers GR, Schiffman JD, Rotter V, Malkin D, Shlien A
Nat Commun 2023 Jan 5;14(1):77. doi: 10.1038/s41467-022-35727-y. PMID: 36604421Free PMC Article
Batchala PP, Eluvathingal Muttikkal TJ, Mukherjee S
Radiol Clin North Am 2021 May;59(3):471-500. doi: 10.1016/j.rcl.2021.01.009. PMID: 33926690
Swaminathan M, Bannon SA, Routbort M, Naqvi K, Kadia TM, Takahashi K, Alvarado Y, Ravandi-Kashani F, Patel KP, Champlin R, Kantarjian H, Strong L, DiNardo CD
Cold Spring Harb Mol Case Stud 2019 Feb;5(1) Epub 2019 Feb 1 doi: 10.1101/mcs.a003210. PMID: 30709875Free PMC Article
Stoffel EM
Gastroenterol Clin North Am 2016 Sep;45(3):509-27. doi: 10.1016/j.gtc.2016.04.008. PMID: 27546846
Coffin CM, Davis JL, Borinstein SC
Histopathology 2014 Jan;64(1):68-87. Epub 2013 Nov 18 doi: 10.1111/his.12280. PMID: 24236688

Therapy

Ilanchezhian M, Varghese DG, Glod JW, Reilly KM, Widemann BC, Pommier Y, Kaplan RN, Del Rivero J
Front Endocrinol (Lausanne) 2022;13:961650. Epub 2022 Oct 31 doi: 10.3389/fendo.2022.961650. PMID: 36387865Free PMC Article
Ottaviano M, Giunta EF, Rescigno P, Pereira Mestre R, Marandino L, Tortora M, Riccio V, Parola S, Casula M, Paliogiannis P, Cossu A, Vogl UM, Bosso D, Rosanova M, Mazzola B, Daniele B, Palmieri G, Palmieri G
Int J Mol Sci 2021 Jul 2;22(13) doi: 10.3390/ijms22137160. PMID: 34281219Free PMC Article
Ricker CA, Woods AD, Simonson W, Lathara M, Srinivasa G, Rudzinski ER, Mansoor A, Irwin RG, Keller C, Berlow NE
Cold Spring Harb Mol Case Stud 2021 Feb;7(1) Epub 2021 Feb 19 doi: 10.1101/mcs.a005983. PMID: 33436392Free PMC Article
Raimundo L, Ramos H, Loureiro JB, Calheiros J, Saraiva L
Biochim Biophys Acta Rev Cancer 2020 Jan;1873(1):188339. Epub 2020 Jan 7 doi: 10.1016/j.bbcan.2020.188339. PMID: 31917206
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Semin Oncol 2016 Feb;43(1):134-145. Epub 2015 Sep 7 doi: 10.1053/j.seminoncol.2015.09.015. PMID: 26970132Free PMC Article

Prognosis

Ilanchezhian M, Varghese DG, Glod JW, Reilly KM, Widemann BC, Pommier Y, Kaplan RN, Del Rivero J
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Frebourg T, Bajalica Lagercrantz S, Oliveira C, Magenheim R, Evans DG; European Reference Network GENTURIS
Eur J Hum Genet 2020 Oct;28(10):1379-1386. Epub 2020 May 26 doi: 10.1038/s41431-020-0638-4. PMID: 32457520Free PMC Article
Guha T, Malkin D
Cold Spring Harb Perspect Med 2017 Apr 3;7(4) doi: 10.1101/cshperspect.a026187. PMID: 28270529Free PMC Article
Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM, Wrensch MR, Barnholtz-Sloan JS
Neuro Oncol 2014 Jul;16(7):896-913. doi: 10.1093/neuonc/nou087. PMID: 24842956Free PMC Article
Olivier M, Hollstein M, Hainaut P
Cold Spring Harb Perspect Biol 2010 Jan;2(1):a001008. doi: 10.1101/cshperspect.a001008. PMID: 20182602Free PMC Article

Clinical prediction guides

Light N, Layeghifard M, Attery A, Subasri V, Zatzman M, Anderson ND, Hatkar R, Blay S, Chen D, Novokmet A, Fuligni F, Tran J, de Borja R, Agarwal H, Waldman L, Abegglen LM, Albertson D, Finlay JL, Hansford JR, Behjati S, Villani A, Gerstung M, Alexandrov LB, Somers GR, Schiffman JD, Rotter V, Malkin D, Shlien A
Nat Commun 2023 Jan 5;14(1):77. doi: 10.1038/s41467-022-35727-y. PMID: 36604421Free PMC Article
Frebourg T, Bajalica Lagercrantz S, Oliveira C, Magenheim R, Evans DG; European Reference Network GENTURIS
Eur J Hum Genet 2020 Oct;28(10):1379-1386. Epub 2020 May 26 doi: 10.1038/s41431-020-0638-4. PMID: 32457520Free PMC Article
Guha T, Malkin D
Cold Spring Harb Perspect Med 2017 Apr 3;7(4) doi: 10.1101/cshperspect.a026187. PMID: 28270529Free PMC Article
Bougeard G, Renaux-Petel M, Flaman JM, Charbonnier C, Fermey P, Belotti M, Gauthier-Villars M, Stoppa-Lyonnet D, Consolino E, Brugières L, Caron O, Benusiglio PR, Bressac-de Paillerets B, Bonadona V, Bonaïti-Pellié C, Tinat J, Baert-Desurmont S, Frebourg T
J Clin Oncol 2015 Jul 20;33(21):2345-52. Epub 2015 May 26 doi: 10.1200/JCO.2014.59.5728. PMID: 26014290
Olivier M, Hollstein M, Hainaut P
Cold Spring Harb Perspect Biol 2010 Jan;2(1):a001008. doi: 10.1101/cshperspect.a001008. PMID: 20182602Free PMC Article

Recent systematic reviews

Freycon C, Lupo PJ, Witkowski L, Budd C, Foulkes WD, Goudie C
Pediatr Blood Cancer 2023 Nov;70(11):e30651. Epub 2023 Aug 28 doi: 10.1002/pbc.30651. PMID: 37638828
Lo Piccolo L, Jantrapirom S, Moonmuang S, Teeyakasem P, Pasena A, Suksakit P, Charoenkwan P, Pruksakorn D, Koonrungsesomboon N
Trop Med Int Health 2021 Nov;26(11):1401-1410. Epub 2021 Oct 4 doi: 10.1111/tmi.13673. PMID: 34478609
Warby M, Wakefield CE, Vetsch J, Tucker KM
Clin Genet 2019 Jan;95(1):140-150. Epub 2018 Oct 10 doi: 10.1111/cge.13442. PMID: 30191952
Forbes Shepherd R, Lewis A, Keogh LA, Werner-Lin A, Delatycki MB, Forrest LE
J Adolesc Young Adult Oncol 2018 Oct;7(5):525-545. Epub 2018 Jul 13 doi: 10.1089/jayao.2018.0028. PMID: 30004834
Borges LM, Ayres FM
Genet Mol Res 2015 Dec 16;14(4):17034-43. doi: 10.4238/2015.December.16.4. PMID: 26681051

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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2023
      UK NICE Clinical Guideline CG164, Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer, 2023

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