Abstract

BackgroundThe clinical phenotype associated with germline SMARCB1 mutations has as yet not been fully documented. It is known that germline SMARCB1 mutations may cause rhabdoid tumor predisposition syndrome (RTPS1) or schwannomatosis. However, the co‐occurrence of rhabdoid tumor and schwannomas in the same patient has not so far been reported.MethodsWe investigated a family with members harboring a germline SMARCB1 deletion by means of whole‐body MRI as well as high‐resolution microstructural magnetic resonance neurography (MRN). Breakpoint‐spanning PCRs were performed to characterize the SMARCB1 deletion and its segregation in the family.ResultsThe index patient of this family was in complete continuous remission for an atypical teratoid/rhabdoid tumor (AT/RT) treated at the age of 2 years. However, at the age of 21 years, she exhibited paraparesis of her legs and MRI investigations revealed multiple intrathoracic and spinal schwannomas. Breakpoint‐spanning PCRs indicated that the germline deletion segregating in the family encompasses 6.4‐kb and includes parts of SMARCB1 intron 7, exons 8–9 and 3.3‐kb located telomeric to exon 9 including the SMARCB1 3′ UTR. The analysis of sequences at the deletion breakpoints showed that the deletion has been caused by replication errors including template‐switching. The patient had inherited the deletion from her 56‐year‐old healthy mother who did not exhibit schwannomas or other tumors as determined by whole‐body MRI. However, MRN of the peripheral nerves of the mother's extremities revealed multiple fascicular microlesions which have been previously identified as indicative of schwannomatosis‐associated subclinical peripheral nerve pathology.ConclusionThe occurrence of schwannomatosis‐associated clinical symptoms independent of the AT/RT as the primary disease should be considered in long‐term survivors of AT/RT. Furthermore, our investigations indicate that germline SMARCB1 mutation carriers not presenting RTs or schwannomatosis‐associated clinical symptoms may nevertheless exhibit peripheral nerve pathology as revealed by MRN.

Highlights

  • The clinical phenotype associated with germline SMARCB1 mutations has as yet not been fully documented

  • We report the follow-up of a patient (II.4, Figure 1) with a germline SMARCB1 deletion of exons 8–9 who survived an atypical teratoid/rhabdoid tumor (AT/Rhabdoid tumors (RTs)) treated at the age of 2 years without tumor recurrence as determined by analysis of the patient at the age of 17 years (Kordes et al, 2014)

  • We report the follow-up of female patient II.4 with a germline SMARCB1 deletion who survived an atypical teratoid (AT)/RT surgically removed at the age of 2 years (Kordes et al, 2014)

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Summary

Introduction

The clinical phenotype associated with germline SMARCB1 mutations has as yet not been fully documented. Only four families have been reported, with germline SMARCB1 mutation carriers being either affected by schwannomatosis or RT (Table 1) (Carter et al, 2012; Eaton et al, 2011; Sredni & Tomita, 2015; Swensen et al, 2009). We report the follow-up of a patient (II.4, Figure 1) with a germline SMARCB1 deletion of exons 8–9 who survived an AT/RT treated at the age of 2 years without tumor recurrence as determined by analysis of the patient at the age of 17 years (Kordes et al, 2014).

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