Li-Fraumeni Syndrome Clinical Presentation

Updated: Nov 29, 2023
  • Author: Avanthi Tayi Shah, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
  • Print


Patients should be counseled about the signs and symptoms of cancer.  They should be encouraged to report any unusual findings, as these may relate to a cancer presentation.

Some authors have advocated for genetic screening in children who are diagnosed with specific cancers, irrespective of family history, including adrenocortical carcinoma and choroid plexus carcinoma at any age, osteosarcoma, rhabdomyosarcoma before age 3 years or rhabdomyosarcoma with diffuse anaplasia, hypodiploid acute lymphoblastic leukemia (ALL), and Sonic Hedgehog (SHH) subtype of medulloblastoma, as several groups have documented a 10-100% rate of germline TP53 mutations in these subsets. [10, 7, 29, 30, 31, 32]

Early age of onset of cancer, positive family history, and multiple primary malignancies suggest a hereditary cancer syndrome.

Obtaining a thorough family history with particular emphasis on cancer can be tedious, but it is an important part of the evaluation of every child diagnosed with a malignancy.

Because of the significantly increased risk of cancer associated with Li-Fraumeni syndrome (LFS), obtaining a thorough family cancer history over at least 3 generations is very important. The history should screen for all tumor types, with particular attention to soft-tissue sarcomas, osteosarcoma, brain tumors, leukemia, and adrenal cortical carcinoma. Occasionally, family history only becomes positive after several years; therefore, updating the family cancer history is important.

Birch and colleagues found that the probands in families with significant cancer history are more likely to be males younger than 24 months at time of diagnosis and are more likely to have tumors with embryonic histologic findings when compared with other children (not affected by Li-Fraumeni syndrome) diagnosed with soft-tissue sarcomas. [33]

Birch et al also showed that mothers of children with soft-tissue sarcomas and osteosarcomas have a 3-fold increased risk of developing breast cancer at young ages. [34]

Curtin et al used the Utah Population Database to look at first-, second-, and third-degree family members of 4482 pediatric subjects with cancer diagnosed before age 19 years over a 43-year period, compared with matched population controls. They showed that first-degree siblings of pediatric cancer cases faced a 2-fold increased risk of a pediatric cancer diagnosis, with the risk increasing to 3.6-fold if the child was diagnosed prior to age 5 years. Although first-degree relatives of pediatric cases have a slightly increased risk of adult tumors, when they do develop cancer they have a 1.7-fold risk of developing a tumor in the Li-Fraumeni spectrum. [35]



Physical Examination

No specific physical findings are attributed to individuals affected by Li-Fraumeni syndrome other than the findings related to the presentation of specific cancers.

Physical findings related to specific cancers are as follows:

  • Breast lump (breast cancer)

  • Neurologic changes including seizures, headaches, vomiting, and gait abnormalities (brain cancers)

  • Formation of a soft-tissue mass (soft-tissue sarcoma) or a bone-related mass (bone sarcoma)

  • Fevers, pancytopenia, fatigue, pallor, bruising, bleeding, bone pain (acute leukemia)

  • Signs of virilization including prepubertal genital hair, clitoromegaly or increased penile size, deep voice, and acne associated with an abdominal mass (adrenal cortical carcinoma)

Annual physical examination as part of well care should be performed, including detailed skin and neurological assessments.  [36]

Breast self-examination training and regular monthly breast self-examination, starting at age 18 years. [36]

Clinical breast examination should be performed every 6-12 months, starting at age 20-25 years. [36]

In patients with an identified TP53 mutation, when a tumor may arise is unknown; thus, having a physician with whom one has an established relationship may assist in noting changes in the physical examination.