Neurofibromatosis

Timothy C. Hain, MD DizzinessTumor index Page last modified: September 11, 2009

Neurofibromatosis is the name given to two distinct genetic disorders characterized by cutaneous tumors, or neurofibromas.

Neurofibromatosis type 1, or NF1, occurs in 1 in 3000 individuals. It is the result of a genetic defect in chromosome 17. About half of all cases are inherited in an autosomal dominant fashion, and the other half are sporadic. Typical manifestations include:

cafe au lait spots
cutaneous tumors
plexiform lesions
axillary freckling
Lisch nodules of the iris
Optic gliomas
Bony abnormalities

NF2 is rare; there are only several thousand affected individuals in the entire United States, corresponding to about 1 in 40,000 individuals (see image below). Roughly 5% of patients with acoustic neuroma have type II neurofibromatosis. More information about NF2 can be found at http://ghr.nlm.nih.gov/gene=nf2

NF-2 is inherited in an autosomal dominant fashion. The defect in NF-2 is in chromosome 22.

Criteria for diagnosis of NF-2 include:

1) bilateral acoustic neuromas, or 2) first-degree relative with NF-2 and either a unilateral lesion, or two of the following: neurofibroma, meningioma, glioma, schwannoma, and a juvenile posterior subcapsular opacity.

Diagnosis of acoustic neuroma associated with NF2


Axial image of patient with NF2 showing acoustic neuromas on both sides (Image courtesy of Dr. Richard Wiet).	Higher image showing multiple meningiomas in same patient with NF2.

Acoustic neuroma caused by type-II neurofibromatosis should be suspected in young patients and those with a family history of neural tumors. The figure above shows an example of such a person. It is common in this disease to become deaf due to bilateral acoustic neuromas. Genetic testing for NF1 and NF2 is available commercially, for example, from Athena Diagnostics.

Treatment of NF2

Treatment of acoustic neuroma's generally follows the same principles as treatment of acoustic neuroma that arise sporadically. As tumors are usually multiple, and may arise on the opposite side, there is an attempt to do as little damage as possible.

A recent report suggests that NF2 may be treated medically with bevacizumab,

an antibody to vascular endothelial growth factor (VEGF) (Plotkin et al, 2009). We hope that this treatment method is confirmed to be effective as well as financially feasible. Most treatments with monoclonal antibodies are extremely expensive.

References

Evans, D. G., A. Moran, et al. (2005). "Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought." Otol Neurotol26(1): 93-7.
Massuda A and others. Hearing changes after diagnosis in neurofibromatosis type 2. Otol Neurotol 25:150-154, 2004
Neurofibromatosis. NIH consensus dev conference consensus statement 1987;6(12) 1-7
.Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, Halpin C, Padera TP, Tyrrell A, Sorensen AG, Jain RK, di Tomaso E. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, Halpin C, Padera TP, Tyrrell A, Sorensen AG, Jain RK, di Tomaso E.N Engl J Med. 2009 Jul 23;361(4):358-67. Epub 2009 Jul 8.