NORD gratefully acknowledges Kristina Bundra, Pharm. D, NORD Editorial Intern, Madeline Zupan, NORD Editorial Intern from the University of Notre Dame, and D Gareth Evans, MD, FRCP, Director, Neurofibromatosis Clinic, Central Manchester Foundation NHS Trust Regional Genetic Service, St Mary's Hospital, Manchester, UK, for assistance in the preparation of this report.
The characteristic symptoms of NF2 usually develop around the time of puberty or during early adulthood. These symptoms may include problems with balance, buzzing or ringing in the ears (tinnitus), and/or gradual hearing loss. These symptoms usually result from the presence of benign tumors on both auditory nerves (acoustic neuromas vestibular schwannomas). Almost all affected individuals develop bilateral vestibular schwannomas by age 30 years. Other tumors of the central nervous system may also develop, and can include neurofibromas, meningiomas, low grade gliomas (mainly benign ependymomas of the spinal cord), and schwannomas.. The size, location, and number of tumors may vary in different people affected. (For more information on tinnitus, choose “tinnitus” as your search term in the Rare Disease Database.)
Individuals with NF2 may also develop cloudiness on the lenses of the eyes (posterior capsular cataracts) at a younger age than would otherwise be expected. Symptoms of cataracts may include impaired vision, and, in some cases, the progressive loss of vision. (For more information on this disorder, choose “cataracts” as your search term in the Rare Disease Database.)
People with NF2 generally have fewer brown spots (café-au-lait) on the skin than those who have NF1. Affected individuals may also experience spasms of the facial muscles; generalized muscle weakness, numbness, pain, and/or partial paralysis; difficulty swallowing; and/or impaired speech. Other neurological problems may also develop including headaches and/or seizures.
In some individuals with NF2, the disorder is inherited as an autosomal dominant trait. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.
In other individuals with NF2, there is no family history of the disease. In such cases, NF2 is caused by new (sporadic) genetic changes (mutations) that appear to occur for unknown reasons.
NF2 results from mutations of a gene located on the long arm of chromosome 22 (22q12.2). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered.
The NF2 gene regulates (encodes for) the production of a protein known as merlin/schwannomin that plays a role in suppressing the development of certain tumors (tumor suppressor). According to investigators, merlin/schwannomin is related to a class of proteins (ezrin-radixin-moesin proteins) that serve to link the internal, supportive system within a cell (cytoskeleton) to proteins in cell membranes. Several different mutations of the NF2 gene have been identified in individuals with the disorder (e.g., deletions, nonsense and frameshift mutations). Investigators suggest that different mutations of the gene may contribute to the wide variability of symptoms and findings in affected individuals.
NF2 is a rare disorder that affects males and females in equal numbers. All races and ethnic groups are equally affected by this disorder. The estimated incidence of NF2 is 1 in 33,000 people worldwide. The symptoms of this disease typically become apparent during puberty or early adulthood. The average age of onset is 18 to 24 years.
The diagnosis of NF2 is confirmed by a thorough clinical evaluation and specialized testing (i.e., CT scan, magnetic resonance imaging (MRI), pneumoencephalogram, or arteriogram are very rarely used nowadays). Molecular genetic testing for mutations in the NF2 gene is available for most affected individuals who have a positive family history.
The treatment of acoustic neuromas associated with NF2 is the surgical removal of the tumors, when possible. The surgical procedure that is performed is based upon the size and precise location of the tumors. Radiation therapy may be considered for some individuals with this disorder, especially those who are not candidates for surgery. The VEGF inhibitor bevacizumab may also be considered to treat rapidly growing schwannomas but is very expensive.
Other treatment is symptomatic and supportive.
Regular monitoring may be required for affected or at-risk individuals. An annual magnetic resonance imaging (MRI) may be necessary beginning at approximately age 10 to 12 years and continuing until at least the fourth decade of life in addition to regular hearing evaluations. Earlier diagnosis and better treatment lend itself to improved survival in those affected.
Genetic counseling can be beneficial for people with NF2 and their families.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For more information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruiting Office:
Tollfree: (800) 411-1222
TTY: (866) 411- 1010
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
The Children’s Tumor Foundation launched an NF Registry in 2012. The purpose of this registry is to find people who may be eligible for clinical trials or other research studies being conducted in the field of NF, and to determine the commonality of specific NF characteristics. Please go to www.nfregistry.org for more information
RareConnect offers a safe patient-hosted online community for patients and caregivers affected by this rare disease. For more information, visit www.rareconnect.org.
Slattery, WH. Neurofibromatosis Type 2.OtolaryngolClin North Am. 2015 Jun; 48(3): 443-460.
Choi JW, Lee JY, Phi JH, et al. Clinical course of vestibular schwannoma in pediatric neurofibromatosis type 2. J NeurosurPediatr. 2014 Jun; 13(6): 650-7.
Cosetti MK, Golfinos JG, Roland JT. Quality of Life (QoL) Assessment in Patients with Neurofibromatosis Type 2 (NF2).Otolaryngol Head Neck Surg. 2015 Mar 16.
Vranceanu AM, Merker VL, Park E, et al. Quality of life among adult patients with neurofibromatosis 1, neurofibromatosis 2 and schwannomatosis: a systematic review of the literature. J Neurooncol. 2013 Sep; 114(3): 257-62.
Merker VL, Bredella MA, Cai W, et al. Relationship between whole-body tumor burden, clinical phenotype, and quality of life in patients with neurofibromatosis. Am J Med Genet A. 2014 Jun; 164A(6): 1431-7.
Kontorinis G, Nichani J, Freeman Sr, et al. Progress of hearing loss in neurofibromatosis type 2: implications for future management. Eur Arch Otorhinolaryngol.2014 Oct. 8.
Hilton DA, Hanemann CO. Schwannomas and their pathogenesis. Brain Pathol. 2014 Apr; 24(3): 205-20.
Schulz A, Zoch A, Morrison H. A neuronal function of the tumor suppressor protein merlin.ActaNeuropatholCommun. 2014 Jul 12; 2:82.
Lloyd SK, Evans DG. Neurofibromatosis type 2 (NF2): diagnosis and management. HandbClin Neurol. 2013; 115: 957-67.
Aboukais R, Bonne NX, Baroncini M, et al. Management of multiple tumors in neurofibromatosis type 2 patients. Neurochirugie. 2015 Jun 9.
Maniakas A, Saliba I. Neurofibromatosis type 2 vestibular schwannoma treatment: a review of the literature, trends, and outcomes. OtolNeurotol. 2014 Jun: 35(5): 889-94.
Szudek J, Briggs R, Leung R. Surgery for neurofibromatosis 2. CurrinOpinOtolaryngol head Neck Surg. 2012 Oct; 20(5): 347-52.
Lin Al, Gutmann DH.Advances in the treatment of neurofibromatosis-associated tumours. Nat Rev ClinOncol. 2014 Nov; 10(11): 616-24.
PlotkinSr, Bredella MA, Cai W, et al. Quantitative assessment of whole-body tumor burden in adult patients with neurofibromatosis.PLoS One. 2012; 7(4).
Hochart A, Gaillard V, Baroncini M, et al. Bevacizumab vestibular schwannomas growth rate in children and teenagers with neurofibromatosis type 2. J Neurooncol. 2015 May 29.
Monteiro TA, Goffi-Gomez MV, Tsuji RK, et al. Neurofibromatosis 2: hearing restoration options. Braz J Otorhinolaryngol. 2012 Oct; 78(5): 128-34.
Wolters PL, Martin S, Merker VL, et al. Patient-reported outcomes in neurofibromatosis and schwannomatosis clinical trials. Neurology. 2013 Nov 19; 81:S6-14.
Evans DG. Neurofibromatosis 2. 1998 Oct 14 Updated 2011 Aug 18]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.Available at: http://www.ncbi.nlm.nih.gov/books/NBK1201/. Accessed June 9, 2015.
Neurofibromatosis type 2. Genetics Home Reference (GHR).Reviewed December 2013.Available at: http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-2. Accessed June 9, 2015.
Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 101000;Updated2012 Nov 2. Available at: http://omim.org/entry/101000. Accessed June 9, 2015.
Evans G. Neurofibromatosis type 2. Orphanet. Available at: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=637.0. Last update: June 2009. Accessed June 24, 2015.
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