What Is Schwannomatosis?
Neurofibromatosis is not a single medical disorder. It refers to three different conditions involving the development of tumors that may affect the brain, spinal cord and the nerves that send signals between the brain and spinal cord and all other parts of the body. Most tumors are non-cancerous (benign), although some may become cancerous (malignant).
The conditions are:
- Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease
- Neurofibromatosis type 2 (NF2)
- Schwannomatosis (SWN)
Schwannomatosis (SWN) is the rarest form of the three conditions and is genetically and clinically distinct from NF1 and NF2. In many cases, mutation of the SMARCB or LZTR1 genes is associated with the disease; however, the genetic cause of SWN in some people is unknown.
Causes of Schwannomatosis
The reason neurofibromatosis tumors develop in NF1, NF2 and schwannomatosis isn't known, but it appears to be caused in part by mutations in genes that play key roles in suppressing growth in nervous system cells. These mutations keep these genes from making normal proteins that control the ability of the cells to function properly. Without the normal function of these proteins cell growth increases, leading to the formation of tumors.
Risk Factors for Schwannomatosis
Couples with a family history of neurofibromatosis and schwannomatosis should discuss their risk factors with medical professionals before becoming pregnant. With the guidance of a genetic counselor, options may include working with an egg or sperm donor, adoption, in utero tests (such as chorionic villus sampling or amniocentesis) or pre-implantation genetic tests (for those becoming pregnant using IVF).
Neurofibromatosis occurs in both biological sexes and in all races and ethnic groups. Why tumors develop in these conditions isn't completely known, but it appears to be caused in part by mutations in genes that play key roles in suppressing growth in nervous system cells. These mutations keep the genes — identified as NF1, NF2, SMARCB1 and LZTR1 — from making normal proteins that control the ability of the cells to function properly. Without the normal function of these proteins cell growth increases, leading to the formation of tumors.
Screening for & Preventing Schwannomatosis
It may be impossible to distinguish someone with NF2 from SWN based on clinical features alone. Genetic testing may be needed to correctly diagnose individuals with features of these conditions who lack a known family history or bilateral vestibular schwannomas (those that occur on both sides of the body). Genetic testing can be useful in some situations, such as for prenatal testing or when the clinical diagnosis is inconclusive.
Detailed imaging of the brain and spinal cord by MRI is necessary, and additional imaging based on symptoms may reveal schwannomas on peripheral nerves.
Signs & Symptoms of Schwannomatosis
Signs and symptoms of schwannomatosis (SWN) significantly overlap with those of NF2 since they result from the development of slow-growing schwannomas of the cranial, spinal and peripheral nerves and in some cases meningiomas of the brain and spinal cord. About one-third of individuals with schwannomatosis have tumors limited to a single part of the body, such as an arm, leg or a segment of the spine. Some people develop many tumors, while others develop only a few. Schwannomas or meningiomas in the setting of schwannomatosis sometimes show no symptoms.
Other symptoms of SWN a doctor may look for are:
- Chronic pain anywhere on the body. Chronic pain affects many people with SWN; this pain may or may not be associated with a specific schwannoma.
- Numbness, tingling or weakness in the fingers and toes and/or loss of muscle function
Diagnosing Schwannomatosis
It may be impossible to distinguish someone with NF2 from SWN based on clinical features alone. Genetic testing may be needed to correctly diagnose individuals with features of these conditions who lack a known family history or bilateral vestibular schwannomas (those that occur on both sides of the body). Genetic testing can be useful in some situations, such as for prenatal testing or when the clinical diagnosis is inconclusive.
Detailed imaging of the brain and spinal cord by MRI is necessary, and additional imaging based on symptoms may reveal schwannomas on peripheral nerves.
Treating Schwannomatosis
There is no currently accepted medical treatment or drug for schwannomatosis. Surgery may help some people with growing tumors or symptoms that are directly referred to as individual schwannomas. However, the potential risk of nerve damage must be weighed carefully against potential benefits of surgery.
Living with Schwannomatosis
Current basic and clinical research is not only aimed at understanding how genetic defects cause the diverse conditions and medical problems encountered by people with schwannomatosis, but also how to predict which clinical features will arise in any given person (personalized or precision medicine). In addition, studies in NF1, NF2 and SWN have revealed numerous important insights for investigators working in other fields, including brain cancer, sarcoma, autism, learning disabilities, nerve regeneration, chronic pain and targeted therapies.
Ongoing research continues to discover additional genes and molecular pathways that may play a role in neurofibromatosis-related tumor suppression or growth. Continuing research is starting to reveal how this novel family of growth regulators controls how and where tumors form and grow, which may lead to the development of new drugs and therapies for schwannomatosis.