Molecular diagnostic challenges in a case with atypical teratoid tumor: Case report

Abstract Atypical teratoid rhabdoid tumors comprise 2%–3% of central nervous system tumors in children; over 90% occur before 3 years of age. It is classified as a grade IV tumor according to the World Health Organization. Herein we present the diagnostic challenges associated with an ATRT with a new inherited germline mutation. Six-month-old male with a family history of a deceased brother due to a CNS tumor. An MRI reported a posterior fossa tumor, ventriculoperitoneal shunt, and a 90% tumoral resection with 1.5 cc residual tumor was achieved, diagnosing a non-metastatic, atypical teratoid rhabdoid tumor with tissue SMARCB1 loss, high risk for age. Next-generation sequencing for SMARCB1 was performed, and a novel synonymous variant of uncertain significance c.69C>T was identified at exon 1. It was inherited from the asymptomatic 32-year-old father, the mother and two sisters were not carriers. After chemotherapy and radiotherapy, the patient had a spine relapse and died at 2 years 9 months. The finding of a germline SMARCB1 mutation confirms the RTPS diagnosis in our patient. This case highlights the importance of molecular studies, however, there are challenges when interpreting the results, there is lack of evidence to conclude the pathogenic nature of variants. Synonymous variants are not expected to have a phenotypic impact, but there is growing evidence that these types of changes may alter the protein's function, especially in cancer. Incomplete penetrance is also a remarkable finding that has been frequently described for families with RTPS.