Neurofibromatosis 2 50% de novo mutations Paternal Age ??

Disease characteristics. Neurofibromatosis 2 (NF2) is characterized by bilateral vestibular schwannomas with associated symptoms of tinnitus, hearing loss, and balance dysfunction. The average age of onset is 18 to 24 years. Almost all affected persons develop bilateral vestibular schwannomas by the age of 30 years. Affected indivduals may also develop schwannomas of other cranial and peripheral nerves, meningiomas, and rarely, ependymomas and astrocytomas. Posterior subcapsular lens opacities that rarely progress to a visually significant cataract are the most common ocular findings. Mononeuropathy that occurs in childhood is an increasingly recognized finding; it frequently presents as a persistent facial palsy, a squint (third nerve palsy), or hand/foot drop.

Diagnosis/testing. Diagnosis of NF2 is based on clinical criteria. NF2f is the only gene known to be associated with neurofibromatosis type 2. Confirmatory molecular genetic testing of the NF2 gene is clinically available. The main role of molecular genetic testing is in early detection of at-risk individuals (primarily the children of classically affected individuals) for the purpose of medical management and surveillance. Prenatal diagnosis is clinically available.

Management. Treatment of vestibular schwannoma is primarily surgical. Stereotactic radiosurgery, most commonly with the gamma knife, may be an alternative to surgery. Management of individuals with vestibular tumors should include counseling for insidious problems with balance and underwater disorientation, which can result in drowning. Radiation therapy of NF2-associated tumors should be carefully considered since radiation exposure, especially in childhood, may induce, accelerate, or transform tumors. Treatment for hearing loss includes referral to an audiologist, lip-reading and sign language instruction, and possibly hearing aids and/or cochlear or brain stem implants. Individuals with visual impairment require routine, complete eye examinations. Surveillance for affected or at-risk individuals includes annual MRI beginning around age ten to 12 years and continuing until at least the fourth decade of life. Hearing evaluation including BAER testing may also be useful.

Genetic counseling. NF2 is inherited in an autosomal dominant manner. About 50% of individuals with NF2 have an affected parent and 50% have NF2 as the result of a de novo gene mutation. However, 25-30% of those representing simplex cases (i.e., individuals with no family history of NF2) are mosaic for an NF2 mutation. The risk to the sibs of the proband depends upon the genetic status of the parents. If a parent of the proband is affected, the risk to the sibs is 50%. Prenatal testing is clinically available. The disease-causing allele of an affected family member must be identified or linkage established in the family before prenatal testing can be performed.