# Molecular pathogenesis of the schwannomatosis genes and genetic testing strategies

## TL;DR

This paper reviews the genetic causes of schwannomatosis and how genetic testing can help diagnose and manage the condition.

## Contribution

The paper provides a detailed comparison of the three schwannomatosis genes and their associated clinical and genetic features.

## Key findings

- NF2, LZTR1, and SMARCB1 are schwannomatosis genes located on chromosome 22.
- Each gene is associated with distinct clinical features and tumor characteristics.
- Genetic testing is essential for accurate diagnosis, especially in mosaic disease cases.

## Abstract

The three major schwannomatosis genes, NF2, LZTR1 and SMARCB1, are all located within approximately 9 megabases on chromosome 22 and cause three genetically distinct conditions with significant clinical phenotypic overlap. All forms of schwannomatosis predispose to the development of multiple schwannomas, but display differences in tumour location and long-term prognosis. In addition, high levels of mosaic disease can complicate clinical diagnosis. Genetic diagnosis can be critical for distinguishing between the three conditions to optimise clinical management, especially in cases of mosaic disease. This review summarises the distinctions between the clinical and genetic characteristics of each form of schwannomatosis and discusses the genetic analytic tools that are typically used to detect the variants found in these conditions.