Phakomatoses are a group of neurocutaneous disorders characterised by involvement of structures that arise from the embryonic ectoderm (thus central nervous system, skin and eyes). Other organs may also be involved

Clinical presentation

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.

Neoplasms

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:

• 
  pheochromocytoma
  
• 
  malignant peripheral nerve sheath tumour (MPNST)
  
  • 
    previously known as neurofibrosarcoma
    
  • 
    overal risk of developing a MPNST is ~10%⁷
    
• 
  Wilms tumour
  
• 
  rhabdomyosarcoma
  
• 
  renal angiomyolipoma
  
• 
  glioma
  
  • 
    juvenile pilocytic astrocytoma
    
  • 
    optic nerve glioma
    
  • 
    diffuse brainstem glioma
    
  • 
    spinal astrocytoma and spinal pilocytic astrocytoma ⁹
    
• 
  carcinoid tumour(s)
  
• 
  leiomyoma(s)
  
• 
  leiomyosarcoma
  
• 
  ganglioglioma
  
• 
  leukaemia
  

Pathology

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) - 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