Schwannomatosis (SWN) is the least common and most recently identified form of NF. The term schwannomatosis is an umbrella term for several genetic conditions that cause the development of benign tumors to grow on nerves. Some types of SWN affects 1 in 20,000 people, with NF2-related schwannomatosis (NF2) the most common type of SWN. Excluding NF2, the other types of SWN affect just 1 in 70,000 individuals.
Schwannomatosis is a type of NF in which individuals develop tumours, called schwannomas, on nerves in the central nervous system (brain and spine) and on peripheral nerves, which are the nerves throughout the rest of the body. Most tumours are not cancerous as is the case for the other neurofibromatoses.
There are at least three genes, NF2, LZTR1, and SMARCB1 that are known to cause schwannomatosis, and there may be additional genes discovered in the future. These genes are thought to help regulate cell growth and division. If these genes are not functioning properly, the cells may multiply excessively and form tumours.
This page focuses on the less common forms of SWN.
CLICK HERE to learn more about NF2-related schwannomatosis, or NF2.
signs and symptoms
Signs of schwannomatosis usually occur in adulthood, between the ages of 20 and 40, although they can occur at any age.
Schwannomas are typically slow growing and located deep inside the body.
The most common symptom is chronic pain, which can occur anywhere in the body and often may not relate to a tumour.
The intensity and frequency of pain varies significantly among individuals who are affected, and, in some cases, the size of the tumour does not necessarily relate to the intensity level of the pain.
Schwannomatosis is a variable condition. While most people with schwannomatosis experience some degree of pain that requires medical management, a small number of people have only mild pain. Some people with schwannomatosis develop many tumours throughout their body, while others may have only one or two tumours during their lifetime.
In addition, a small subset of individuals develop tumors along the hearing/balance nerves (called vestibular schwannoma or VS).
Although pain is the most common symptom, other signs can include:
- Vision changes, and
- Swollen areas under the skin where tumours have formed.
The former diagnostic criteria for schwannomatosis (and NF2) classified patients primarily based on clinical features, however, it is now apparent that the symptoms of these conditions span the same continuum. For this reason, "schwannomatosis" no longer defines a distinct syndrome, but is now used as an umbrella term to describe the overlapping conditions in which a patient has many schwannomas.
All types of schwannomatosis are a result of a change in a gene (a sequence of DNA) located on chromosome 22. When a gene changes in a way that keeps it from working correctly, it is called a pathogenic variant (formerly called a gene mutation). Therefore, the different types of SWN are named by identifying the pathogenic variant that is the cause of the diagnosis, like so: GENE-related schwannomatosis (gene names are in italics).
So far, scientists have identified the following types of schwannomatosis:
- NF2-related schwannomatosis
- SMARCB1-related schwannomatosis
- LZTR1-related schwannomatosis
- 22q-related schwannomatosis
- Schwannomatosis NOS (not otherwise specified)
- Schwannomatosis NEC (not elsewhere classified)
As pain is often the main and presenting symptom, it may take several years before schwannomatosis is diagnosed and the source of the pain is identified. The degree of pain and tumors vary widely and some symptoms of schwannomatosis are shared with other conditions.
Diagnostic criteria for SMARCB1-related schwannomatosis or LZTR1-related schwannomatosis
A diagnosis of SMARCB1-related schwannomatosis or LZTR1-related schwannomatosis can be made when a patient meets one of the following criteria:
- At least one pathologically confirmed schwannoma or hybrid nerve sheath tumor AND a SMARCB1 or LZTR1 pathogenic variant in an unaffected tissue such as blood or saliva
- A common SMARCB1 or LZTR1 pathogenic variant in two anatomically distinct schwannomas or hybrid nerve sheath tumors
Note: diagnosis requires surgical specimen.
Diagnostic criteria for 22q-related schwannomatosis
A diagnosis of 22q-related schwannomatosis can be made when an individual doesn’t meet criteria for NF2-related schwannomatosis, SMARCB1-related schwannomatosis, or LTZR1-related schwannomatosis, and has both of the following molecular features:
- Loss of heterozygosity (LOH) of the same chromosome 22q markers in two anatomically distinct schwannomas or hybrid nerve sheath tumors AND
- A different NF2 pathogenic variant in each tumour that can’t be detected in unaffected tissue
Note: diagnosis requires at least two surgical specimens
Diagnostic criteria for schwannomatosis-NOS (not otherwise specified)
A diagnosis of schwannomatosis-NOS (not otherwise specified) can be made if both of the following criteria are met and genetic testing was not performed or is not available:
- Presence of two or more lesions on appropriate imaging consistent with non-intradermal schwannomas, and
- Pathologic confirmation of at least one schwannoma or hybrid nerve sheath tumour.
Diagnostic criteria for schwannomatosis-NEC (not elsewhere classified)
A diagnosis of schwannomatosis-NEC (not elsewhere classified) can be made if both of the above criteria are met and genetic testing does not reveal a pathogenic variant in known schwannomatosis-related genes.
management and treatment
There is currently no cure for schwannomatosis, and no medication that has been shown to be effective in treating schwannomas.
Management of the condition is based on each person’s concerns.
Monitoring schwannomatosis usually involves scans to assist specialists with monitoring the location, size and effects of tumours. These can include:
As pain is one of the most common symptoms of this condition pain relief such as Gabapentin, Pregabalin, short-acting opioids or non-steroidal anti-inflammatory drugs may be successful for many people with this condition.
Surgery is utilised for schwannomas that are causing symptoms other than pain, but due to the risk of further neurological complications is often used as a last resort.
Disclaimer: We have taken all reasonable steps and care to ensure that the information on this page is medically accurate and up-to-date at the time of writing. The Children's Tumour Foundation cannot be liable should this information change with new research. Please always consult your individual healthcare specialist for advice about your specific condition and needs.