Li-Fraumeni syndrome

Introduction

First reported in 1969 by Frederick Li & Joseph Fraumeni from the National Cancer Institute.

Epidemiology

• rare, 1 in 5000-20,000 families
• early age of the cancer diagnosis with ~1/2 of affected individuals diagnosed with cancer < 30 years of age

Pathology

• so-called SBLA tumors
  • sarcoma, breast, bone, brain, lung, larynx, leukemia liver & adrenal cortex tumors
• mutated p53 has longer 1/2life than normal p53
  • tumors stain positively for p53

Genetics

• p53 chromosomal aberrations autosomal dominant (70% of families)
  • 25% with sporadic p53 mutations
• CHEK2 chromosomal aberrations
  • cancer risk in carriers of CHEK2 mutation may be far less than p53 mutation
• associated with defects in CDKN2A

Diagnostic criteria

• sarcoma diagnosed < 45 years of age
• 1st degree relative with any cancer < 45 years of age
• 1st degree or 2nd degree relative with any cancer < 45 years of age
• other criteria & criteria for Li-Fraumeni-like syndrome

Laboratory

• TP53 gene mutation
• CHEK2 gene mutation
• complete blood count (CBC) every 4 months for leukemia or lymphoma
• erythrocyte sedimentation rate & serum lactate dehydrogenase every 4 months

Diagnostic procedures

• colon cancer:
  • colonoscopy very 2 years, beginning at age 25-30 or 10 years before the earliest known colon cancer in the family

Radiology

• breast MRI & clinical breast examination twice a year, starting at age 20 to 25, or 5 to 10 years before the earliest known breast cancer diagnosis in the family
• brain tumor: annual brain MRI
• soft tissue & bone sarcoma:
  • annual whole-body MRI
  • ultrasound of abdomen & pelvis every 6 months

* a TP53 genetic mutation can cause a person to have an increased sensitivity to therapeutic (ionizing) radiation

• if possible, people with a germline TP53 mutation should avoid or minimize exposure to diagnostic radiation

Management

• annual dermatology (skin) examination for melanoma

More general terms

• hereditary neoplastic syndrome; cancer susceptibility syndrome

More specific terms

• Li Fraumeni syndrome 2 (CHK2 mutation associated)
• Li Fraumeni syndrome/TP53 mutation associated

Additional terms

• breast cancer
• cellular tumor antigen p53; tumor suppressor p53, phosphoprotein p53; antigen NY-CO-13 (TP53, p53)
• checkpoint kinase 2; serine/threonine protein kinase Chk2; homolog of S. cerevisiae Rad53; Cds1 (CHEK2, CHK2, RAD53)
• Li-Fraumeni syndrome genotyping

Patient information

Li Fraumeni syndrome patient information

Database

• OMIM: https://mirror.omim.org/entry/151623