Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android. Learn more here!



  • Autosomal dominant condition with incidence of 1 in 3000 live births.

  • Diagnosed clinically if 2 major features are present (see Table 135-1).

  • Cutaneous neurofibromas:

    • Softer than the surrounding connective tissue and protrude just above the skin surface or lie just under the skin with an overlying violaceous hue.

  • Subcutaneous neurofibromas:

    • Arise from peripheral nerves, both under the skin and deep in the viscera.

    • Generally much harder.

  • Plexiform neurofibromas:

    • Generally present at birth or apparent during the first several years of life.

    • May lead to disfigurement, blindness (secondary to amblyopia, glaucoma, or proptosis), loss of limb function, or organ dysfunction by compression of vital structures.

  • Mosaic neurofibromatosis Type 1 (segmental NF-1):

    • Manifestations of NF-1, usually limited to one area of the body.

    • Occurs as result of a postconceptional mutation in the NF1 gene, leading to somatic mosaicism.


A consensus development conference was held by the National Institutes of Health in 1987 to establish diagnostic criteria to promote better clinical research and care of patients with neurofibromatosis Type 1 (NF-1).1 The 7 diagnostic features recognized at this conference (Table 135-1), and the recommendation that 2 or more of these 7 features be present before a diagnosis of NF-1 is established, have proven extremely useful and continue to be used without modification more than 30 years later. Perhaps the one caveat is the identification of a separate autosomal dominant syndrome caused by an inactivating mutation of the gene encoding sprouty-related EVH1 domain-containing protein 1 (SPRED1), which leads to the development of café-au-lait spots, intertriginous freckling, and macrocephaly, but none of the other manifestations of NF-1 (Legius syndrome).2

Table 135-1Diagnostic Criteria for Neurofibromatosis Type 1a


Café-au-lait spots, which are flat, pigmented macules, are often the first manifestation of NF-1 to appear (Fig. 135-1). Frequently present at birth, they become more numerous as the infant grows; new ones may continue to appear throughout the first decade of life. Once noticed, they tend to grow in size in proportion to the overall growth of the child. Although infrequently found on the face, they may be noted ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.