Complex Inheritance Patterns

Although schwannomatosis is a genetic condition, the inheritance patterns for this disorder are complex and much less clear than for both NF1 and NF2. Some cases of schwannomatosis are familial, with more than one person in a family sometimes being affected with the disorder. People who are the first in their family to be diagnosed with schwannomatosis are known as sporadic cases. Another form of the disorder – called mosaic or segmental schwannomatosis – causes features to appear only on one side or one part of the body. Also, schwannomatosis seems to skip generations, sometimes affecting distant family members of an individual who has the disorder.

Genetic Mutation and Recent Discovery of New Gene for Schwannomatosis

A mutation in a gene first identified in 2007 – called SMARCB1 – is associated with about 40% of familial cases and 10% of sporadic cases of schwannomatosis. For many people with schwannomatosis, a mutation in the SMARCB1 gene is not the cause of their condition. Research conducted at the UAB Medical Genomics Laboratory – which specializes in genetic studies for all forms of neurofibromatosis – has recently led to the groundbreaking discovery of a new gene, called LZTR1, that helps to explain some familial and sporadic cases of schwannomatosis in people who don’t have a mutation in the SMARCB1 gene. A sophisticated gene sequencing technique was used to identify the LZTR1 gene and to determine that a mutation in this gene predisposes individuals to develop schwannomatosis. The identification of the new LZTR1 gene and mutation has led to the development of genetic testing that can help to confirm a diagnosis of schwannomatosis in some people who do not have a mutation in the SMARCB1 gene.