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Background: Neurofibromatosis type 1 and neurofibromatosis type 2 are unrelated, distinct genetic disorders characterized by the development of central and peripheral nervous system tumors., Summary: Neurofibromatosis type 1 is the most common inherited tumor predisposition syndrome with a lifelong increased risk of benign and malignant tumor development, such as glioma and nerve sheath tumors. Neurofibromatosis type 2 classically presents with bilateral vestibular schwannoma, yet it is also associated with non-vestibular schwannoma, meningioma, and ependymoma. Historically, the number of effective therapies for neurofibromatosis-related neoplasms has been limited., Key Message: In the past decade, there have been significant advances in the development of precision-based therapies for NF-associated tumors with an increased emphasis on functional outcomes in addition to tumor response. Continued scientific discovery and advancement of targeted therapies for NF-associated neoplasms are necessary to continue to improve outcomes for patients with NF., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by the development of tumors of the nervous system and is associated with NF2 gene alterations. Atypical teratoid rhabdoid tumor (ATRT) is a malignant central nervous system tumor that occurs primarily in children less than 3 years of age. The majority of cases of ATRT demonstrate genomic alterations of SMARCB1, a core member of the SWI/SNF chromatin-remodeling complex and tumor suppressor gene. SMARCB1 inactivation in ATRT is occasionally associated with somatic NF2 deletion; however, concurrent germline NF2 mutations have not been reported. Herein, we describe the case of a 3-year-old patient who presented with an intracranial mass. Next generation sequencing analysis of tumor identified homozygous deletions of the entire SMARCB1 gene and exon 7 to exon 14 of NF2 gene with whole chromosome 22 loss of heterozygosity (LOH). Multiplex Ligation-dependent Probe Amplification (MLPA) assay performed on blood identified a germline heterozygous intragenic deletion of NF2 exon 7 to exon 14; a somatic chromosome 22 LOH led to the homozygous deletion. SMARCB1 MLPA assay of blood showed no deletion. This cascade represents a novel, "four-hit" mechanism of SMARCB1 inactivation resulting in ATRT and the first known dual diagnosis of NF2 and ATRT., (Copyright © 2021 Elsevier Inc. All rights reserved.)