Neurofibromatosis-1

Descriptive text is not available for this imageBASICS

DESCRIPTION

  • 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 or two or more abnormalities in the choroid (vascular layer of the eye)
    • Optic pathway glioma
    • Osseous lesions, including sphenoid wing dysplasia, dysplasia of a long bone (most commonly tibia)
    • A pathogenic NF1 variant revealed by genetic testing
    • A parent with NF-1 based on the criteria above
  • *At least one of the two pigmentary manifestations must be present on both sides of the body.
ALERT

Note: Neurofibromatosis type 2 (NF-2) is a much less common 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.

EPIDEMIOLOGY

Incidence

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

Prevalence

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

RISK FACTORS

Genetics

  • 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 the same mutation.
    • NF1 gene, which codes for neurofibromin, is located on chromosome 17q11.2.
  • No known racial/ethnic predisposition
  • Course impossible to predict except in several circumstances
    • Deletion of whole NF1 gene may lead to early appearance and large numbers of cutaneous or subcutaneous neurofibromas, more significant 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.
    • Mutations within several distinct codons in the NF1 gene may lead to either manifestations of Noonan syndrome (e.g., distinctive facies, pulmonary valve stenosis, pectus excavatum) or a more severe phenotype characterized by multiple spinal neurofibromas and a higher risk of malignancy.

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