Neurofibromatosis type 1

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a multisystem neurocutaneous disorder, the most common phakomatosis, and a RASopathy. Additionally, it is also one of the most common inherited CNS disorders, autosomal dominant disorders and inherited tumour syndromes. 

Individual systemic manifestations are discussed individually: 

The remainder of this article pertains to a general discussion of neurofibromatosis type 1 (NF1). 

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 two or more of following are required 2:

In addition ~45% (range 30-60%) of patients have learning disabilities, and approximately 1% have hypertension due to renal artery stenosis.

It is important to consider that NF1 has a much earlier age of onset than schwannomatosis and NF2, with approximately 50% of patients meeting the diagnostic criteria for NF1 by the age of 1 year and approximately 97% meeting the criteria by the age of 8 years 10

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:

The NF1 gene locus is on chromosome 17q11.2 and the gene product is neurofibromin, which acts as a tumour suppressor of the Ras/MAPK pathway; inactivation of the gene thus predisposes to tumour development 6,12. For this reason, the disorder is classified as a RASopathy 12.

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. 

  • localised neurofibroma (cutaneous neurofibroma): the most common type, is a focal lesion that typically is located in the dermis and subcutis
  • diffuse neurofibroma (subcutaneous neurofibroma): localised 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 
  • FASI (focal areas of signal intensity): occur in deep white matter and basal ganglia or corpus callosum 5, areas of T2/FLAIR hyperintensity with no contrast enhancement
  • optic nerve glioma or optic pathway glioma (may manifest as enlarged optic foramen)
  • progressive sphenoid wing dysplasia
  • lambdoid suture defects
  • dural calcification at vertex
  • moya moya phenomenon (rare)
  • buphthalmos
  • cutaneous and subcutaneous neurofibromas: benign peripheral nerve sheath tumours

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.  

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Article information

rID: 1725
Section: Syndromes
Synonyms or Alternate Spellings:
  • Neurofibromatosis type 1 (NF1)
  • Neurofibromatosis type 1
  • NF1
  • von Recklinghausen disease
  • neurofibromatosis type I
  • Type neurofibromatosis

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Cases and figures

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    Cor T2
    Case 1: plexiform neurofibroma
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    Case 2: plexiform neurofibroma
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    Case 2: neurofibromata
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    Neurofibromatosis...
    Case 4: cutaneous neurofibromata
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    Case 5: with optic nerve gliomas
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    Case 6: with cord compression
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    Plexiform neurofi...
    Case 7: hemifacial hypertrophy
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    NF1

Multiple ner...
    Case 8: ribbon-ribs deformity
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    Case 9: neurofibromas in breast and axilla
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    Case 10: sphenoid wing dysplasia
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    Case 11: with ulnar pseudoarthrosis
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    T2 AXI: Plexiform...
    Case 13: plexiform neurofibroma of thigh
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    Case 14: neurofibromas
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    Case 15: neurofibromas dorsal nerve roots
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    Case 17: intraspinal neurofibroma
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    Case 18: plexiform neurofibroma of foot
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    Case 19: plexiform neurofibroma femoral nerve
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    There is a parave...
    Case 20
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    Case 21
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    Case 22: huge abdominal and retroperitoneal plexiform neurofibromatosis
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