P3A353: Beneath the Tissue: A Genetic Cause of Migratory Pain in an Athlete

Introduction: Extremity pain in an athlete is most commonly due to some sort of injury, trauma, or external force. Here we present a case of a 14-year-old multi-sport athlete with migratory pain from a genetic cause.

Case Description: A 14-year-old male multi-sport athlete with a past medical history significant for familial p53 mutation presents to sports medicine clinic with 3 weeks of migratory pain and weakness. His primary complaint is left thigh pain. He was previously evaluated at an orthopedic clinic and an emergency room. His family history is significant for an older sister with a history of p53 mutation and rhabdomyosarcoma, and mother with a history of p53 mutation, currently undergoing treatment for breast cancer. An MRI Left Femur was obtained and showed a diffuse marrow replacing process affecting entire left femur, left tibial plateau and bony pelvis with periosteal reaction about the left femur shaft, small left hip joint effusion, and edema in adjacent muscle (Image 1 & 2).

Discussion: Li-Fraumeni syndrome is a cancer predisposition syndrome. It is caused by a germline mutation of TP53 gene on chromosome 17p13.1. This mutation has autosomal dominant pattern of inheritance with high penetration. Patients with this mutation have a very high lifetime cumulative risk of developing early-onset malignancies. The syndrome is named for Drs. Frederick Li and Joseph F. Fraumeni Jr., who first reported four families of children with rhabdomyosarcoma or other soft tissue malignancies affecting their parents and relatives at a young age. Since that time, brain tumors, osteosarcoma, leukemia, and adrenal cortical carcinoma have joined rhabdomyosarcoma as part of the syndrome.

The classic clinical characterization of Li-Fraumeni Syndrome by Li and Fraumeni includes an initial patient with a sarcoma, a first-degree relative with cancer before the age of 45 years, and a first or second-degree relative with cancer before the age of 45 years or a sarcoma at any age. Since then, families with similar features, but not meeting the full criteria for Li-Fraumeni Syndrome, have been identified using two different sets of criteria proposed by Birch et al, Eeles, and Chompret et al. The Birch et al criteria do not require the initial presentation of a sarcoma. The Eeles criteria only require two first- or second-degree relatives with Li-Fraumeni Syndrome component tumors at any age. The patient we presented in this case had a known p53 germline mutation, however he meets the diagnosis of Li-Fraumeni Syndrome by both Birch and Eeles criteria.

Conclusion: He was admitted to the oncology service for further evaluation and biopsy. His bone marrow biopsy showed High-Risk Pre-B Cell Acute Lymphoblastic Leukemia. He continues to receive continuation chemotherapy per St. Jude Total XVI due to his very high-risk status secondary to severe hypodiploidy.