eMedicine Specialties > Pediatrics: General Medicine > Oncology

Li-Fraumeni Syndrome: Differential Diagnoses & Workup

Author: Kavita Patel, MD, Clinical Postdoctoral Fellow in Pediatric Hematology and Oncology, Department of Pediatrics, Baylor College of Medicine
Coauthor(s): Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA; Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories
Contributor Information and Disclosures

Updated: Dec 1, 2008

Differential Diagnoses

Acute Lymphoblastic Leukemia
Gardner Syndrome and Other Intestinal Polyposis Syndromes
Acute Myelocytic Leukemia
Late Effects of Childhood Cancer and Treatment
Adrenal Carcinoma
Nonrhabdomyosarcoma Soft Tissue Sarcomas
Astrocytoma
Osteosarcoma
Bioethics in Pediatric Practice
Retinoblastoma
Childhood Cancer, Epidemiology
Rhabdomyosarcoma
Childhood Cancer, Genetics
WAGR Syndrome
Chromosomal Breakage Syndromes
Wilms Tumor

Other Problems to Be Considered

Families with Li-Fraumeni-like (LFL) syndrome have (1) a proband younger than 45 years with childhood cancer or sarcoma, brain tumor, or adrenal cortical carcinoma; (2) first-degree or second-degree relative with a typical LFL cancer occurring at any age; and (3) another first-degree or second-degree relative in the lineage younger than 60 years diagnosed with any cancer. Only approximately 20% of LFL kindreds have demonstrable germline TP53 mutations. Much less stringent criteria for LFL familial cancer predisposition include 2 first-degree or second-degree relatives with Li-Fraumeni (LFS)-related malignancies (sarcoma, breast cancer, malignant brain tumor, adrenal cortical carcinoma, acute leukemia) at any age.

Breast and ovarian cancer family syndrome with genetic mutations of BRCA1 or BRCA2 may be in the differential diagnosis.

Workup

Laboratory Studies

Evaluation for constitutional TP53 mutation in patients with cancer and a family history or presentation suggestive of potential Li-Fraumeni syndrome (LFS) cancer predisposition is warranted to aid in predicting future risk of other primary malignancies for the patient and other family members.

Although most reported Li-Fraumeni syndrome–related TP53 mutations occur in exons 5-8, optimal DNA analysis should include evaluation of the entire coding and noncoding portions of the gene (exons 1-11) by automated sequencing methods. Because TP53 mutations are constitutional (ie, germline), DNA derived from any clinical source can potentially be evaluated. Peripheral blood leukocytes are the most easily obtained source and are typically collected in citrate or heparin anticoagulant tubes.

Imaging Studies

Mammography screening of females in Li-Fraumeni syndrome kindreds is advocated by some but remains controversial. To be most effective, serial mammograms are initiated at an early age (late teens to early twenties). Some debate surrounds the accuracy of mammographic findings in identifying small masses in the breasts of young women due to increased tissue density. Breast MRI screening beginning at age 20-25 years has also been advocated.

Experimental evidence suggests potential increased cancer risk due to increased adverse effects of ionizing radiation on Li-Fraumeni syndrome cells with TP53 defects.

More on Li-Fraumeni Syndrome

Overview: Li-Fraumeni Syndrome
Differential Diagnoses & Workup: Li-Fraumeni Syndrome
Treatment & Medication: Li-Fraumeni Syndrome
Follow-up: Li-Fraumeni Syndrome
References
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References

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  2. Varley JM, McGown G, Thorncroft M, Santibanez-Koref MF, Kelsey AM, Tricker KJ. Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Cancer Res. Aug 1 1997;57(15):3245-52. [Medline].

  3. Tabori U, Nanda S, Druker H, Lees J, Malkin D. Younger age of cancer initiation is associated with shorter telomere length in Li-Fraumeni syndrome. Cancer Res. Feb 15 2007;67(4):1415-8. [Medline].

  4. Shlien A, Tabori U, Marshall CR, et al. Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome. Proc Natl Acad Sci U S A. Aug 12 2008;105(32):11264-9. [Medline].

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Further Reading

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Keywords

Li-Fraumeni syndrome, LFS, LFL kindred, p53 mutation, Li-Fraumeni–like kindred, germline mutation, p53 tumor suppressor gene mutation, TP53, TP53 tumor suppressor gene mutation, breast cancer, brain tumor, acute leukemia, soft tissue sarcoma, osteosarcoma, adrenal cortical carcinoma, sarcoma, Ewing sarcoma

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Contributor Information and Disclosures

Author

Kavita Patel, MD, Clinical Postdoctoral Fellow in Pediatric Hematology and Oncology, Department of Pediatrics, Baylor College of Medicine
Kavita Patel, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, Phi Beta Kappa, and Texas Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA
Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories
Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Stephan A Grupp, MD, PhD, Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania
Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Timothy P Cripe, MD, PhD, Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center
Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida, Clinical Professor, Department of Pediatrics, UNC, Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Executive Director, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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