EPCO-44. RHABDOID TUMOR PREDISPOSITION SYNDROME DUE TO A GERMLINE SMARCB1 MUTATION IN TWO INFANT SIBLINGS

Abstract

Abstract INTRODUCTION Rhabdoid tumors (RTs) are highly aggressive malignancies caused by a loss–of–function mutation in the SMARCB1 tumor suppressor gene on chromosome 22 that makes up the SW1/SNF chromatin remodeling complex involved in gene transcription. In rhabdoid tumor predisposition syndrome (RTPS), a biallelic germline SMARCB1 mutation markedly increases the risk of affected individuals developing early, aggressive, and rapidly progressing RTs, most commonly in the CNS, referred to as atypical teratoid rhabdoid tumors (AT/RT), and the kidneys, but oftentimes presents with synchronous lesions. In this case series, we present a family affected by RTPS with a recurrence of AT/RT in two infant siblings with the same germline SMARCB1 mutation. CASE SERIES DESCRIPTION An 8-month-old female was brought to the emergency department for 3 months of vomiting, developmental regression, and CN VI palsy. Brain imaging revealed a posterior fossa mass, acquired obstructive hydrocephalus, and spinal metastasis. Four years later, her 3-month-old sister was also brought in for evaluation for 2 months of vomiting, irritability, increasing head circumference, and vertical gaze palsy. Her brain imaging similarly showed a posterior fossa mass and acquired obstructive hydrocephalus, but no metastasis. Both siblings underwent subtotal tumor resections and ventriculoperitoneal shunt placement followed by chemotherapy. While on active treatment, they experienced rapid disease progression and ultimately succumbed to their illness. Genetic testing on the family identified the same in-frame deletion in the SNF5 homology domain of SMARCB1 and loss of heterozygosity of chromosome 22 in the two sisters; their mother was found to be a carrier. CONCLUSION This case series describes a family affected by RTPS, demonstrating the risk of familial recurrence in SMARCB1 germline mutations and emphasizing the need for genetic testing and counseling for these families should they wish to have additional children.