What is Neurofibromatosis?

Neurofibromatosis Type 1 (NF1)

Neurofibromatosis (NF) is a term applied to two important autosomal dominant human disorders that involve the disordered growth of cells of neural crest origin. Neurofibromatosis 1, also known as von Recklinghausen neurofibromatosis, is one of the most frequent dominant disorders in man, affecting ~1 in 3,000 births. A hallmark of NF1 is its variability of symptoms, which include abnormally pigmented skin patches (cafe-au-lait spots), iris hamartomas (Lisch nodules), and benign neurofibromas (peripheral nerve tumors consisting mainly of Schwann cells with fibroblasts, mast cells, and other cellular elements) that may be profoundly disfiguring. About 5% of NF1 patients develop malignant peripheral nerve sheath tumors (malignant neurofibrosarcomas) that are often fatal. NF1 patients show increased risk for several other tumors, such as optic gliomas, astrocytomas and juvenile malignant myeloid disorders, making it a familial cancer syndrome. Other frequent features of NF1 are learning disabilities and skeletal abnormalities. NF1 is caused by inactivating mutations in a tumor suppressor gene on chromosome 17q which encodes neurofibromin, a large protein with a RasGTPase activating domain that implicates it as a regulator of signal transduction.

Neurofibromatosis Type 2 (NF2)

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.

Schwannomatosis

Schwannomatosis is a third form of NF that has only recently been recognized.  The incidence is estimated to be ~1 in 40,000 with familial occurence uncommon as up to 90% of people have apparently sporadic disease.  Persons with schwannomatosis develop multiple schwannomas on cranial, spinal and peripheral nerves, but they do not develop vestibular tumors and do not go deaf. Unlike other forms of NF, affected individuals do not develop other types of tumors and do not have learning disabilities. Like NF2, the tumors are benign.  Persons with schwannomatosis usually have much greater problem with pain than with neurological disability although, as with all forms of NF, schwannomatosis may vary greatly among patients. 

Questions? Contact the Webmaster