Abstract
Atypical teratoid rhabdoid tumors (ATRT) are aggressive, malignant tumors of the central nervous system (CNS) that develop due to a loss-of-function mutation in the SMARCB1 gene. Rhabdoid tumor predisposition syndrome (RTPS) is characterized by familial cases as a result of pathogenic germline variants of this gene and an increased risk of developing ATRT within the first 2 years of life, which carries a poor prognosis. Genetic penetrance is incomplete with variable expressivity but the patient's age at time of diagnosis remains the most significant indicator of survival. We present a case of RTPS in a sibship born to unaffected parents, one of which was a carrier. The first sibling was diagnosed at 8 months of age after presenting with vomiting, developmental regression, and CN VI palsy for 3 months. Imaging revealed a posterior fossa mass, acquired obstructive hydrocephalus, and spinal metastasis. Four years later, her 3-month-old sister was brought in for evaluation due to vomiting, irritability, and macrocephaly for 2 months, along with a new vertical gaze palsy. Imaging findings also showed a posterior fossa mass and acquired obstructive hydrocephalus but without metastasis. Both siblings underwent craniotomy with subtotal tumor resection and ventriculoperitoneal shunt placement. Chemotherapy was promptly initiated but despite active treatment, they had rapid disease progression and ultimately passed away. Whole exome sequencing of both patients revealed an in-frame deletion involving the SNF5 homology domain of SMARCB1, with consistent findings on whole transcriptome sequencing, and evidence of loss of a single copy of chromosome 22. In this case report, we present a family faced with the devastating outcomes of RTPS and emphasize the importance of genetic testing and counseling for these families after diagnosis in the first child. Families should also be streamlined to a fertility specialist prior to subsequent pregnancies as an opportunity for familial screening.