• Neurofibromatosis type 1 (NF-1) is an autosomal dominant tumor suppressor gene disorder.
  • NF-1 is diagnosed based on the presence of any two of the following National Institutes of Health (NIH) Consensus Conference diagnostic criteria:
    • Six or more café au lait spots, at least 1.5 cm in diameter in postpubertal individuals or 0.5 cm in diameter in prepubertal individuals
    • Inguinal or axillary freckling
    • Two or more cutaneous neurofibromas or one plexiform neurofibroma
    • Two or more iris Lisch nodules
    • Optic nerve glioma
    • Osseous lesions, including sphenoid wing dysplasia, dysplasia of a long bone (most commonly tibia)
    • A 1st-degree relative (parent, sibling, or offspring) with NF-1
Note: Neurofibromatosis type 2 (NF-2) is a rare distinct autosomal dominant tumor suppressor gene disorder characterized by bilateral vestibular schwannomas as well as schwannomas of cranial and peripheral nerves, meningiomas, and ependymomas. It is caused by mutations in the NF2 gene, which codes for a protein known as merlin. This chapter focuses on NF-1.



  • NF-1: 1 in 3,000 live births
  • NF-2: 1 in 33,000 live births


  • NF-1: 1 in 4,000 to 5,000
  • NF-2: 1 in 60,000

Risk Factors


  • Autosomal dominant
    • 50% of the cases are inherited; others occur as sporadic mutations.
    • Penetrance is complete; however, expression is variable even between family members who have same mutation.
    • NF1 gene, which codes for neurofibromin, is located on chromosome 17q11.2.
  • No known ethnic predisposition
  • Course impossible to predict except in two circumstances
    • Deletion of whole NF1 gene leads to early appearance and large numbers of cutaneous neurofibromas, severe cognitive impairment, and dysmorphic features.
    • Three base pair in-frame deletion of exon 17 leads to multiple café au lait spots and intertriginous freckling but no other NF-1 manifestations.

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