Schwannomatosis

Overview

Schwannomatosis is one form of a genetic disorder called neurofibromatosis (NF) that has only recently been recognized. Originally described in Japanese patients, it consists of multiple cutaneous schwannomas, central nervous system tumors, and other neurological complications, excluding hallmark signs of NF. It is a rare disorder, affecting only around 1 in 40,000 individuals.

Schwannomas are mostly benign tumors that commonly occur in individuals with NF2 and schwannomatosis (sometimes called neurofibromatosis type III). Schwann cells are glial cells that myelinate the axons of nerve cells. Myelin is a lipid covering that speeds the conduction of action potentials. When Schwann cells proliferate out of control in an encapsulation it is called a schwannoma. Although schwannomas are benign they become detrimental when the growing tumor compresses the nerve. Schwannomas on sensory nerve axons cause chronic severe pain. Treatment options for schwannomas are to surgically remove them, have radiation, cyberknife or Intracapsular Enucleation. Previous designations for schwannomas include neurinoma and neurilemmoma.

Symptoms

The Schwannomas develop on cranial, spinal and peripheral nerves, symptoms are:

• Chronic pain
• sometimes numbness, tingling and weakness.

About 1/3 of patients have segmental Schwannomatosis, which means that the Schwannomas are limited to a single part of the body, such as an arm, a leg or the spine.

There are several cases where people with Schwannomatosis have developed a vestibular Schwannoma (acoustic neuroma).

Patients with Schwannomatosis do not have learning disabilities related to the disease, symptoms are generally brought on by hormonal changes such as puberty and pregnancy.

Causes

Like the NF1 and NF2 genes, the candidate Schwannomatosis gene, named INI1, is a tumor suppressor that regulates cell cycle, growth and differentiation. INI1 is also known as SMARCB1, hSNF5, or BAF47, and lies on human Chromosome 22. INI1 is also mutated in other tumors including malignant brain & kidney tumors in infants.

Schwannomatosis is known to be a genetic disorder, however it can skip generations.

Diagnosis

Prenatal

Schwannomatosis can not presently be diagnosed prenatally or in the embryo, because the gene for it has not yet been positively identified.

Postnatal

Ferner et al. give the following diagnostic criteria for Schwannomatosis:

1.Definite

• Age >30 years and ≥2 nonintradermal schwannomas, at least one with histologic confirmation and no evidence of vestibular tumor on MRI scan and no known NF mutation, or
• One nonvestibular schwannoma plus a first-degree relative with schwannomatosis

Prognosis

Many of the symptoms of schwannomatosis overlap with NF2.

• Schwannomas occur instead of the neurofibromas that are hallmarks of neurofibromatosis Type 1 (NF1).
• Multiple schwannomas manifest throughout the body or in isolated regions.
• The schwannomas develop on cranial, spinal and peripheral nerves.
• Chronic pain, and sometimes numbness, tingling and weakness.
• About 1/3 of patients have segmental schwannomatosis, which means that the schwannomas are limited to a single part of the body, such as an arm, a leg or the spine.
• There are several cases where people with schwannomatosis have developed a vestibular schwannoma (acoustic neuroma). An acoustic neuroma is a schwannoma on the vestibular nerve in the brain. This nerve is involved in hearing and patients with vestibular schwannomas experience hearing loss. However, bilateral vestibular schwannomas (vestibular schwannomas on both sides of the brain) do not occur in schwannomatosis. Juvenile vestibular tumors do not occur either.
• Patients with schwannomatosis do not have learning disabilities related to the disease.
• Symptoms are sometimes brought on by hormonal changes such as puberty and pregnancy.

Treatment

• Schwannomatosis patients represent 2.4% to 5% of patients undergoing surgical resection of their schwannomas.
• In isolated regions of the body schwannomas are small and difficult to locate. Intraoperative sonography offers invaluable assistance in such cases by localizing small schwannomas and decreasing operative time and extent of the surgical incision.
• If feasible, the schwannomas can be surgically removed. Any tumor-associated pain usually subsides after tumor removal. Damaged nerves and scar tissue can be a result of surgery and pain can be an ongoing problem.
• Sometimes, a tumor will reappear at the same site after surgery.
• If surgery is unfeasible, then pain management will have to be used. Schwannomatosis can sometimes cause severe, untreatable pain over time.
• Other than surgery and/or pain management, there are no other medical treatments available. There are no drugs available to treat Schwannomatosis.
• Gamma knife radiosurgery can be performed on head tumors to help stop growth of a tumor, although there is no guarantee that it will work. The University of Pittsburgh published their experience with over 829 cases and reported 97% of patients had long term tumor control (defined as requiring no further treatment) with Gamma knife radiosurgery.
• Recently, many advances are being made in the treatment of schwannomas. Of interest is CyberKnife, manufactured by Accuray. Success rates, although limited in data, appear to be in the low to mid ninety percent range.
• As most schwannomas are benign, many doctors will take the “watch and wait” approach and leave the tumors alone until they start causing harmful side effects. Schwannomatosis patients have multiple tumors and the risks of having so many surgeries outweigh the benefits