Neurofibromatosis
From Iusmgenetics
Contents |
[edit] Neurofibromatosis
[edit] 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
[edit] Mode of inheritance
- Autosomal dominant with full penetrance, variable expressivity, and pleiotropy
- May also show segmental mosaicism
[edit] Single important gene
- NF1 gene is a tumor suppressor gene that serves to regulate Ras.
- NF1 has a very high mutation rate
[edit] 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
[edit] 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
[edit] Phenotypic information
[edit] Diagnosis
- Typically a clinical dx.