A Novel TP53 Germline Mutation in a Family with a History of Multiple Malignancies: Case Report and Review of the Literature

Objective: Choroid plexus carcinoma (CPC) has been associated with TP53 germline mutations and Li-Fraumeni syndrome (LFS). We describe our finding of a novel germline mutation in the TP53 gene in a family with multiple malignancies and in association with a child presenting with CPC. Method: An 8-month-old male presented with seizure-like activity; imaging disclosed a 1.5-cm left ventricular mass confirmed to be CPC intra- and postoperatively. Family history was significant for a half-sister who died of a primary CNS sarcoma and a paternal grandmother negative for BRCA1, BRCA2, MLH1, and MSH2 mutations with multiple (>6) LFS spectrum malignancies. Results: Familial TP53 testing revealed an A→T substitution at DNA position 13071, creating a deleterious Asn→Ile substitution at amino acid 131 in exon 5. Conclusion: Physicians treating patients with CPC should be attuned to reviewing family history for risk factors suggestive of genetic cancer syndromes such as LFS. These syndromes markedly influence both the patient and family members and may alter postoperative treatment regimens.