Choroid plexus carcinoma in two siblings, with a novel genetic mutation in TP53 – A case report and review of literature

Abstract

Background: Choroid plexus carcinoma (CPC) is an uncommon aggressive neuroectodermal-derived childhood brain malignancy with a dismal prognosis, especially when tumor protein p53 (TP53) mutations or malfunctions are present. The occurrence of these cancers is linked to germline and somatic anomalies at a number of genetic loci. We present a case report of CPC in two siblings which was found to be linked to a unique genetic mutation of TP53 in heterozygous state in both the father and the patient. Case Description: A 2-year-old female child presented with a history of vomiting, headache, and seizures. A brain magnetic resonance imaging discovered a large-sized lesion in the left lateral ventricle with infiltration to surrounding brain parenchyma suggestive of aggressive choroid plexus neoplasm. Her only sibling (sister) died of CPC 1 year ago. Her parents are apparently healthy with no history of the central nervous system malignancies in the maternal and paternal sides. Since two children in a family were affected with CPC, genomic profiling of parents and patients was done. A novel frameshift variant c.72dupA,p. (Leu25Thrfs Ter4) was observed in exon 2 of TP53 in a heterozygous state in the proband. This variant was observed in her father in the heterozygous state. Conclusion: CPC affecting siblings, associated with novel frameshift mutation in TP53 and inherited in an autosomal dominant pattern, is a rare entity. It has importance in genetic counseling and planning targeted molecular treatment. Genetic profiling is important for prognostication, as P53 pathway dysfunction carries a dismal prognosis, especially when it is associated with Li-Fraumeni syndrome.