Schwannomatosis

Schwannomatosis is a rare form of NF that has only recently been recognized and appears to affect around 1:40,000 individuals. As with NF1 and NF2, schwannomatosis may vary greatly between patients. Because of this, and because the population of individuals is so small and the disorder so recently characterized, these patients have, until recently, been hard to definitively identify. Therefore the draft diagnostic criteria below will continue to evolve as more cases are identified and studied.

Features of Schwannomatosis

People with schwannomatosis develop multiple schwannomas on cranial, spinal and peripheral nerves--but they do not develop vestibular tumors and do not go deaf. They also do not develop any other kinds of tumors (for example, meningiomas, ependymomas or astrocytomas) and do not have learning disabilities.

People with schwannomatosis have problems with chronic pain that often exceeds their neurological problems. The first symptom of schwannomatosis is almost always pain, which can occur in any part of the body. Many patients with schwannomatosis go several years before the source of their pain is realized because they have few or no neurological symptoms.

About Schwannomas

Both schwannomas and neurofibromas originate in the insulating covering of peripheral nerves called the nerve sheath. Schwannomas are very homogenous tumors consisting ONLY of nerve sheath cells or Schwann cells. They stay on the outside of the nerve, but may push it aside or against a bony structure causing damage. Neurofibromas are very heterogeneous tumors, which incorporate all sorts of cells and structural elements in addition to the Schwann cells. They infiltrate the nerve and splay apart the individual nerve fibers. Schwannomatosis patients typically do not develop malignancies, although this occurs more frequently in NF1 and NF2.

Genetics

Schwannomatosis is a genetic condition, but unlike NF1 and NF2 it does not have a clear pattern of inheritance. Schwannomatosis often skips generations so that more distant family members with unexplained neurological symptoms and/or unexplained pain should be evaluated for the possibility that they are also affected. In 2007 a candidate gene for schwannomatosis, called INI1, was identified. Since that finding schwannomatosis research has moved forward rapidly and evidence is emerging that the NF2 gene and possibly other genes may also be involved in causing schwannomatosis. Genetic testing for mutations in INI1 is available, though as the role of INI1 and the potential involvement of other genes in schwannomatosis is still being defined, there is as yet no definitive "schwannomatosis genetic test".

Genetics Testing for Schwannomatosis

Medical Genomics Laboratory at University of Alabama, Birmingham: Genetic testing for mutations in INI1 is available, though as noted above, as well as INI1, other genes may be involved in Schwannomatosis. For more information on this, contact the Medical Genomics Laboratory at UAB, phone (205) 934-1520. More information on testing is available at the MGL website.

Is it Schwannomatosis or NF2?

As noted above, those with schwannomatosis do not develop vestibular tumors and do not go deaf. Once a person is found to have multiple schwannomas, the possibility of NF2 must be excluded before a diagnosis of schwannomatosis is given. In an older person with no hearing loss, NF2 is unlikely. In a younger person, or in any person with hearing loss and multiple schwannomas, it is imperative that a high quality MRI scan of the base of the brain be done to exclude the possibility of vestibular tumors and NF2.

Segmental Schwannomatosis

For reasons not yet understood, about 1/3 of patients with schwannomatosis have segmental schwannomatosis, with tumors limited to a single part of the body, such as an arm, a leg or a region of the spine. The tumors of schwannomatosis are relatively slow growing, and probably only need to be imaged when symptoms change.

Clinical Management

Surgical management of schwannomatosis can be effective. When tumors are completely removed, pain often subsides -- although it may recur if new tumors form. When surgery is not feasible, management in a multidisciplinary pain clinic is advisable.

There is no currently accepted medical treatment or drug for schwannomatosis.

In 2005, the first working draft of diagnostic criteria for schwannomatosis were published as a result of the Children's Tumor Foundation's "International Consensus Conference on Schwannomatosis" (Citation: Neurology (2005) 64: 1838-1845).

These criteria are excerpted below. In addition, potential additional diagnostic criteria are included.

Diagnostic Criteria for Schwannomatosis

Individual is age over 30 years
AND has two or more non-intradermal schwannomas, at least one with histological confirmation
AND has no evidence of vestibular tumor on high-quality MRI scan
AND has no known constitutional NF2 mutation

OR

Has one pathologically confirmed non-vestibular schwannoma plus a first-degree relative who meets the above criteria

Possible Additional Diagnostic Criteria for Schwannomatosis:

Individual is age less than 30 years
AND has two or more non-intradermal schwannomas, at lease one with histological confirmation
AND no evidence of vestibular tumor on high quality MRI scan
AND no known constitutional NF2 mutation

OR

Individual is age over 45 years
AND has two or more non-intradermal schwannomas, at least one with histological confirmation
AND has no symptoms of 8th cranial nerve dysfunction
AND has no known constitutional NF2 mutation

OR

Has radiographic evidence of a non-vestibular schwannoma and first degree relative meeting criteria for definite schwannomatosis

Diagnostic Criteria for Segmental Schwannomatosis:
Individuals who meet the above diagnostic criteria (or proposed diagnostic criteria) for schwannomatosis but where this is limited to one limb, or to five or fewer contiguous segments of the spine.

We gratefully acknowledge the contributions to this page from the research of Dr. Mia MacCollin, recently retired, formerly of Harvard Medical School/Massachusetts General Hospital.

Contact Us

Children's Tumor Foundation
120 Wall Street, 16th Floor
New York, NY 10005-3904

Phone: 212-344-6633

info@ctf.org