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

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.