Neurofibromatosis type 2 (NF2) is a rare autosomal dominant neurocutaneous disorder (phakomatosis) manifesting as a development of multiple CNS tumours. Unlike neurofibromatosis type 1 (NF1), it is not associated with neurofibromas. Instead, patients with this disease have:
- intracranial schwannoma(s): mostly vestibular schwannoma(s) sometimes patients may have spinal schwannomas
- intracranial and spinal meningioma(s)
- intraspinal-intramedullary ependymoma(s)
These features give rise to the acronym MISME, which describes Multiple Inherited Schwannomas Meningiomas and Ependymomas 4. In fact, labelling this disorder neurofibromatosis type 2 is a misnomer, because neurofibromas are not a part of its constellation of abnormalities 5.
The disease is rare with an estimated prevalence of 1:50,000. NF2 usually presents in young adults (age 18-24 years) 7.
Of patients with NF2, 50% have an affected parent (autosomal dominant inheritance) and 50% having a de novo mutation 6,7.
The NF2 gene is located on the long arm of chromosome 22 (22q12), and encodes the merlin protein (also known as "schwannomin"). It plays a role in contact inhibition of growth, and has tumour suppressor function at least in part according to this mechanism 9. Although variably expressed throughout the body during human development, merlin is highly expressed in adult neuronal, Schwann, and meningeal cells. Mutations in NF2 cause loss of protein function, resulting in predisposition to tumour formation throughout the nervous system 9.
Although meningiomas are often isolated findings in adults, their presence in a child should raise suspicion regarding NF2. The presence of multiple and different types spinal tumours also raise a high suspicion of NF2 1.
Please refer articles on individual lesions for respective specific imaging features:
- usually an inferior vestibular division of cranial nerve eight
- can also be from the facial nerve
- ependymoma: usually spinal intramedullary (not intracranial/intraventricular)
Bilateral vestibular schwannomas are diagnostic of NF2 7 but care should be taken because bilateral internal acoustic meatus masses are not specific for vestibular schwannoma and can represent, for example, sarcoid or metastases 6.
- 1. Mautner VF, Tatagiba M, Lindenau M et-al. Spinal tumors in patients with neurofibromatosis type 2: MR imaging study of frequency, multiplicity, and variety. AJR Am J Roentgenol. 1995;165 (4): 951-5. AJR Am J Roentgenol (abstract) - Pubmed citation
- 2. Evans DG, Sainio M, Baser ME. Neurofibromatosis type 2. J. Med. Genet. 2000;37 (12): 897-904. J. Med. Genet. (link) - Free text at pubmed - Pubmed citation
- 3. Patronas NJ, Courcoutsakis N, Bromley CM et-al. Intramedullary and spinal canal tumors in patients with neurofibromatosis 2: MR imaging findings and correlation with genotype. Radiology. 2001;218 (2): 434-42. Radiology (full text) - Pubmed citation
- 4. Smirniotopoulos JG, Murphy FM. The phakomatoses. AJNR Am J Neuroradiol. 13 (2): 725-46. AJNR Am J Neuroradiol (citation) - Pubmed citation
- 5. Haaga JR, Boll D. CT and MRI of the whole body. Mosby. (2009) ISBN:0323053750. Read it at Google Books - Find it at Amazon
- 6. Harnsberger HR, Glastonbury CM, Michel MA et-al. Diagnostic Imaging: Head and Neck. Lippincott Williams & Wilkins. (2010) ISBN:1931884781. Read it at Google Books - Find it at Amazon
- 7. 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 from: http://www.ncbi.nlm.nih.gov/books/NBK1201/
- 8. Vargas WS, Heier LA, Rodriguez F, Bergner A, Yohay K. Incidental parenchymal magnetic resonance imaging findings in the brains of patients with neurofibromatosis type 2. NeuroImage. Clinical. 4: 258-65. doi:10.1016/j.nicl.2013.12.010 - Pubmed
- 9. A M Petrilli, C Fernández-Valle. Role of Merlin/NF2 inactivation in tumor biology. (2016) Oncogene. 35 (5): 537. doi:10.1038/onc.2015.125 - Pubmed
- neurofibromatosis type 1 (NF1) (von Recklinghausen disease)
- neurofibromatosis type 2 (NF2) (mnemonic)
- tuberous sclerosis (Bourneville-Pringle disease)
- ataxia telangiectasia
- Sturge-Weber syndrome (encephalotrigeminal angiomatosis)
- von Hippel-Lindau disease (retinocerebellar angiomatosis)
- incontinentia pigmenti (Bloch-Sulzberger syndrome)
- basal cell naevus syndrome (Gorlin-Goltz syndrome)
- Wyburn-Mason syndrome (Bonnet-Dechaume-Blanc syndrome)
- encephalocraniocutaneous lipomatosis
- hypomelanosis of Ito
- Nijmegen breakage syndrome
- epidermal naevus syndrome
- neurocutaneous melanosis
- progressive facial hemiatrophy (Parry-Romberg syndrome)
- PHACE syndrome
- Cowden disease/COLD syndrome
- Gomez-Lopez-Hernandez syndrome