Genetic Risk Factors of Schwannoma Tumors

Posted May 17, 2022

Dr. Miriam Smith, University of Manchester, United Kingdom

Dr. Miriam Smith, University of Manchester, United Kingdom Dr. Miriam Smith

One of the hallmarks of LZTR1-schwannomatosis is multiple schwannomas, a rare type of tumor that forms in the nervous system. These tumors grow from Schwann cells, which are nerve cells within the body. While schwannomas are often benign, they can cause pain that doesn’t respond to drugs. The mechanism of schwannoma formation includes inactivation of the LZTR1 gene on chromosome 22, and the triggering event is thought to require loss of the NF2 gene as well as LZTR1. We know that there are some patients who have a genetic syndrome 22q11.2 deletion syndrome that has not been linked to schwannomas, but involves the deletion of a specific gene region (22q11.2); in a majority of patients with this genetic syndrome, the whole LZTR1 gene is also deleted. Since it is known that approximately 1 in 500 people in the general population will develop a schwannoma and there are no reports of schwannomas in 22q11.2DS, our study has investigated whether whole-gene deletion of LZTR1 occurs in schwannoma development.

With support from a Fiscal Year 2018 NFRP Investigator Initiated Research Award, Dr. Miriam Smith of the University of Manchester has been using a range of genetic techniques to identify the missing heritable elements in a cohort of families with NF1, NF2, or schwannomatosis. One of these studies involved the assessment of genetic testing results for LZTR1-associated schwannomatosis and the clinical phenotypes of patients with 22q11.2DS. There were no reports of schwannoma in over 1,500 patients with 22q11.2DS. In addition, no patients meeting clinical diagnostic criteria for schwannomatosis had a whole-gene deletion in LZTR1. Only 1 patient in 110 with a sporadic inner ear schwannoma had a whole-gene deletion of LZTR1, and the complete mechanism of LZTR1 inactivation remains unknown in this patient. The results suggest that people with a large 22q11.2 deletion may have a reduced risk of developing a schwannoma compared to the general population.

This ongoing work focuses on identifying the underlying cause of disease in well-characterized families with a clinical diagnosis of NF1, NF2, or schwannomatosis in whom no underlying pathogenic variant has yet been found, as well as information pertaining to the mechanism of action of these variants. Additionally the research team hopes to use this information to aid future research into therapeutic drugs.


Evans DG, Messiaen LM, Foulkes WD, Irving REA, Murray AJ, Perez-Becerril C, Rivera B, McDonald-McGinn DM, Stevenson DA, Smith MJ. 2021. Typical 22q11.2 deletion syndrome appears to confer a reduced risk of schwannoma. Genet Med. Sep;23(9):1779-1782. doi: 10.1038/s41436-021-01175-0. Epub 2021 Apr 20. PMID:  33879870; PMCID: PMC8460436.


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Last updated Tuesday, May 17, 2022