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A 44-year-old Hispanic man has neurofibromatosis type 1 (NF-1). He has typical features of NF-1, including eight café-au-lait spots, axillary freckling, and neurofibromas all over his body (Figures 234-1, 234-2, 234-3, and 234-4). He states that he is used to having the NF and it does not currently affect his work or life. He is happily married but never had children. No intervention is necessary at this time other than recommending yearly visits to his family physician and ophthalmologist.

Figure 234-1

A 44-year-old Hispanic man with neurofibromatosis type 1 showing all the typical findings including neurofibromas, café-au-lait spots, and axillary freckling. (Courtesy of Richard P. Usatine, MD.)

Figure 234-2

Close-up of neurofibromas on the back of the man in Figure 234-1. These are soft and round. (Courtesy of Richard P. Usatine, MD.)

Figure 234-3

Large café-au-lait spot on the back of the man in Figure 234-1. Café-au-lait spots are ovoid hyperpigmented macules, 10 to 40 mm in diameter, with smooth borders. (Courtesy of Richard P. Usatine, MD.)

Figure 234-4

Close-up of axillary freckling (Crow sign) with large café-au-lait spot on arm. (Courtesy of Richard P. Usatine, MD.)

NF-1 is a common autosomal dominant disorder that predisposes to tumor formation. Café-au-lait spots are often the first clinical sign. Other clinical signs include neurofibromas, axillary or inguinal freckling, optic gliomas, Lisch nodules, and sphenoid bone dysplasia. Treatment at present is early recognition and monitoring for complications such as cognitive dysfunction, scoliosis or other orthopedic problems, tumor pressure on vital structures, or malignant transformation.

  • NF-1 is relatively common—Birth incidence is 1 in 3000 and prevalence in the general population is 1 in 5000.1
  • Autosomal-dominant inheritance; however, up to 50% of cases are sporadic.1
  • Diagnosis is typically made during childhood.

  • Mutations in the NF-1 gene (on the long arm of chromosome 17) result in loss of function of neurofibromin, which helps keep protooncogene ras (which increases tumorigenesis) in an inactive form.
  • Loss of neurofibromin results in increased protooncogene ras activity in neurocutaneous tissues, leading to tumorigenesis.1

A first-degree relative with NF-1.

For a diagnosis of NF-1, patients need to have at least 2 of the following:2

  1. Two or more neurofibromas (Figures 234-1, 234-2, 234-3, 234-4, 234-5, 234-6) or one or more plexiform neurofibromas (Figure 234-7).

  2. Six or more café-au-lait spots, 0.5 cm or larger before puberty and 1.5 cm or larger after puberty (Figures 234-3 and 234-4).

  3. Axillary or inguinal freckling ...

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