What's neurofibromatosis type 2 (NF2)?
Neurofibromatosis type 2 (NF2) is genetic disorder characterized by the growth of benign tumors of both acoustic nerves (the nerves to the ears). These tumors are called acoustic neuromas or, more precisely, vestibular schwannomas. They cause tinnitus (ringing in the ears), hearing loss, and problems with balance. Other findings in NF2 include schwannomas of other
nerves, meningiomas, and juvenile cataracts. NF2 is inherited in an autosomal dominant manner and is due to mutation in the NF2 gene in chromosome band 22q12.2 which encodes a protein called merlin. About 50% of persons with NF2 inherit it from an affected parent and the other 50% with NF2 have a new gene mutation. Anyone with NF2 has a 50% risk of transmitting it to each of their children. Prenatal testing is available.
Neurofibromatosis 2 is a less common but extremely serious disorder, occurring with an incidence of ~1 in 40,000 persons. The characteristic growth of NF2 is the vestibular schwannoma, a benign, slow growing tumor on the vestibular branch of the acoustic nerve (8th cranial nerve) that can cause loss of hearing and balance, and usually occurs bilaterally. However, other tumors, particularly meningiomas, spinal schwannomas, and ependymomas, are also frequent. In addition, many patients develop posterior subcapsular lens opacities (cataracts). The same tumor types that occur as multiple growths in NF2 also occur as sporadic, solitary tumors in the general population. The tumors of NF2 are histologically benign, but their anatomical locations make management difficult. While they cause functional loss by compressing adjacent nerves, surgical removal often risks permanent nerve damage. The growth of Schwann cells to produce schwannomas or arachnoidal cells to produce meningiomas in NF2 (and in sporadic equivalents) is due to inactivating mutations in a tumor suppressor gene on chromosome 22q, which encodes merlin. Merlin is a 66 kDa protein that shows similarity to the ERM family (ezrin, radixin moesin) that act as linkers between integral membrane proteins and the actin cytoskeleton. Like the ERMs, merlin has an amino-terminal FERM domain (protein 4.1 family domain) and a long carboxyl-terminal alpha helical region, and has been localized to areas of membrane remodeling, suggesting a role in cell communication, adhesion and motility. |
