Neurofibromatosis type 1
Neurofibromatosis type 1 (NF1) or von Recklinghausen disease is a multisystem neurocutaneous disorder and the most common phakomatosis 1. Additionally it is also one of the most common inherited CNS disorders, autosomal dominant disorders and inherited tumour syndromes.
Neurofibromatosis affects 1 : 2500 - 3000 individuals 3. In half of cases, the disease is inherited as an autosomal dominant condition. In the other 50% of cases the disease is due to a new mutation 6. There is variable expression but 100% penetrance by 5 years of age 6.
As is the case with many phakomatoses, NF1 results in a variety of abnormalities of variable severity. To make the clinical diagnosis you require two or more of following2:
- > 6 cafe au lait spots evident during 1 year
- two or more neurofibromas or one plexiform neurofibroma
- optic nerve glioma
- distinctive osseous lesion
- sphenoid wing dysplasia
- two or more iris hamartomas (Lisch nodules)
- axillary or inguinal freckling
- primary relative with NF 1 with above criteria
In addition 30 - 60% of patients have learning disabilities.
It should come as no surprise that a disease due to inactivation of a tumour suppressor gene (see below) is also associated with increased incidence of numerous tumours 1-6:
malignant peripheral nerve sheath tumour (MPNST)
- previously known as neurofibrosarcoma
- overal risk of developing a MPNST is ~10%7
- Wilms tumour
- renal angiomyolipoma
- carcinoid tumour(s)
The NF1 gene locus is on chromosome 17q11.2 and the gene product is neurofibromin, acts as a tumour suppressor; inactivation of the gene thus predisposes to tumour development 6.
The disease primarily is a hamartomatous disorder that involves the ectoderm and mesoderm. Usually three types of neurofibromas occur in this disorder and are distinguished on the basis of their gross and microscopic appearances.
- localized neurofibroma (cutaneous neurofibroma) : the most common type, is a focal lesion that typically is located in the dermis and subcutis
- diffuse neurofibroma (sub cutaneous neurofibroma) : localized in the subcutis, usually in the head and neck region.
- plexiform neurofibroma : considered pathognomonic if present ; they may be seen in virtually any location but usually occur in the neck, pelvis, and extremities
Radiographic and clinical spectrum
- focal areas of signal intensity in deep grey / white matter 5
- optic nerve glioma (manifest with enlarged optic foramen)
- progressive sphenoid wing dysplasia
- lambdoid suture defects
- dural calcification at vertex
- moya moya phenomenon : rare
- posterior vertebral scalloping
- hypoplastic posterior elements
- enlarged neural foramina
- ribbon rib deformity
- rib notching
- dural ectasia
- tibial pseudoarthrosis or less commonly ulnar pseudoarthrosis
- limb hemi hypertrophy
- mediastinal masses
- lung parenchymal disease : ~ 20%
Treatment and prognosis
No single treatment exists, and a combination of supportive and surgical therapies are employed depending on the specific tumours and anomalies present.
Although prognosis is very variable, overall patients with neurofibromatosis type I have a life expectancy approximately half that of non affected individuals, usually succumbing to tumours or cardiovascular complications 8.
- 1. Fortman BJ, Kuszyk BS, Urban BA et-al. Neurofibromatosis type 1: a diagnostic mimicker at CT. Radiographics. 21 (3): 601-12. Radiographics (full text) - Pubmed citation
- 2. Aoki S, Barkovich AJ, Nishimura K et-al. Neurofibromatosis types 1 and 2: cranial MR findings. Radiology. 1989;172 (2): 527-34. Radiology (abstract) - Pubmed citation
- 3. Williams VC, Lucas J, Babcock MA et-al. Neurofibromatosis type 1 revisited. Pediatrics. 2009;123 (1): 124-33. doi:10.1542/peds.2007-3204 - Pubmed citation
- 4. Jacquemin C, Bosley TM, Svedberg H. Orbit deformities in craniofacial neurofibromatosis type 1. AJNR Am J Neuroradiol. 2003;24 (8): 1678-82. AJNR Am J Neuroradiol (full text) - Pubmed citation
- 5. Itoh T, Magnaldi S, White RM et-al. Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities. AJNR Am J Neuroradiol. 1994;15 (8): 1513-9. AJNR Am J Neuroradiol (abstract) - Pubmed citation
- 6. Albright AL, Adelson PD, Pollack IF. Principles and practice of pediatric neurosurgery. Thieme Medical Pub. (2007) ISBN:1588903958. Read it at Google Books - Find it at Amazon
- 7. Ruggieri M. Neurocutaneous Disorders, Phakomatoses & Hamartoneoplastic Syndromes. Springer Verlag. (2007) ISBN:3211213961. Read it at Google Books - Find it at Amazon
- 8. Gupta N, Banerjee A, Haas-Kogan D. Pediatric CNS Tumors. Springer Verlag. (2010) ISBN:3540879765. Read it at Google Books - Find it at Amazon
- 9. Koeller KK, Rushing EJ. From the archives of the AFIP: pilocytic astrocytoma: radiologic-pathologic correlation. Radiographics. 24 (6): 1693-708. doi:10.1148/rg.246045146 - Pubmed citation
Synonyms & Alternative Spellings
|Synonyms or Alternative Spelling||Include in Listings?|
|Neurofibromatosis type 1 (NF1)||✗|
|Neurofibromatosis type 1||✓|
|von Recklinghausen disease||✓|
|neurofibromatosis type I||✗|