Neurofibromatosis 1: Von Recklinghausen’s Disease…

Neurofibromatosis 1 (NF1) is also known as Von Recklinghausen’s Disease.   The neurofibromas of NF1 were first described by Smith in 1849 but Frederick von Recklinghausen was credited with the discovery and coined the name for the disorder in 1882.  NF1 includes more than 85% of all cases of neurofibromatosis.  NF2 is referred to as central or acoustic neurofibrommatosis usually in the absence of skin lesions.  NF3 is associated with schwannnomas and are at higher risk of developing optic gliomas, neurilemmomas and meningiomas.  The incidence of NF1 is 1/3000 to 1/4000 births.

The most common features of NF1 are:

  1. 6 or more Cafe au lait macules (brown macules and patches, similar to large freckles measuring at least 1.5 cm)
  2. Multiple neurofibromas (soft neural tumors that “buttonhole” when pressed on)
  3. Lisch nodules (smooth muscle hamartomas of the iris)
  4. Axillary freckles (Crowe’s sign)

Additional findings in NF1 may include giant pigmented hairy nevi, sacral hypertrichosis, cutis verticis gyrata and macroglosssia.

Large plexiform neurofibromas, such as the one shown above, is virtually pathognomonic for NF1.  On palpation these larger masses resemble a “bag of worms.”  Approximately 50% of NF1 cases are new mutations.  The gene is in the pericentric region of chromosome 17q11.2 and codes for neurofibromin, a protein that negatively regulates signals tranduced by Ras proteins.  Definitive diagnosis requires two or more of the following:

  1. 6 or more cafe au lait macules
  2. 2 or more neurofibromas of any type or 1 plexiform neurofibroma
  3. Axillary freckling
  4. Optic gliomas
  5. 2 or more Lisch nodules
  6. Distinctive osseous lesion such as sphenoid dysplasia or thinning of the long-bone cortex with or without pseudoarthrosis
  7. 1st degree relative (partent, sibling, or offspring) with the disease

Researched was driven when it was believed for many years that Joseph Merrick, the original Elephant Man, had neurofibromatosis.  It has only recently been shown that he had Proteus Syndrome instead.  To read about Proteus Syndrome click HERE.  To read more about NF1 click HERE and HERE.