Neurofibromatosis

From Iusmgenetics

Contents 1 Neurofibromatosis 1.1 General background information 1.2 Mode of inheritance 1.3 Single important gene 1.4 Etiology 1.5 Pathogenesis 1.6 Phenotypic information 1.7 Diagnosis 1.8 Treatment 1.9 Recent research 1.10 5 important facts 1.11 Not to be confused with 1.12 Questions and answers

Neurofibromatosis

General background information

• There are two types (I and II)
  • type I is the most common so that's what we'll describe here
  • Type I = von Recklinhausen Disease
• 1 / 3500
• NF1 demonstrates full penetrance, variable expressivity, and pleiotropy

Mode of inheritance

• Autosomal dominant with full penetrance, variable expressivity, and pleiotropy
• May also show segmental mosaicism

Single important gene

• NF1 gene is a tumor suppressor gene that serves to regulate Ras.
  • NF1 has a very high mutation rate

Etiology

• When NF1 is mutated, it no longer acts as a tumor supressor.
  • 500 known mutations that cause disease
  • 50% of mutations are new to the family when detected in the proband
  • 80% of de novo mutations are paternally derived
    • No age-of-father effect seen in generating these new mutations

Pathogenesis

• NF1 demonstrates pleiotropy, affecting neurological systems, musculoskeletal systems, the eye, and the skin
• Defining features (seen in ~95% of cases):
  • Cafe-au-lait spots
  • Neurofibromas (peripheral nerve tumor; plexiform, subcutaneous, cutaneous)
  • Lisch nodules (pigmented nodules of the iris)
• NF1 pts have increases risk for neoplasms: optic nerve gliomas, brain tumors, malignant myeloid disorders
• Axillary freckling is another important sign

Phenotypic information

Diagnosis

• Typically a clinical dx.

Treatment

Recent research

5 important facts

Not to be confused with

Questions and answers