Neurofibromatosis in Adult
NF1 occurs equally in all ethnicities and among both sexes and is often identified in childhood with the appearance of café au lait macules. The genetic defect is in a tumor suppressor gene on chromosome 17, which codes for neurofibromin, a RAS GTPase activating protein. Patients are at increased risk of developing benign and malignant neoplasms. Benign neoplasms include neurofibromas – complex tumors of admixed Schwann cells, fibroblasts, myelinated and unmyelinated nerve axons, endothelial cells, and mast cells – that occur in 1 of 4 forms: cutaneous, subcutaneous, nodular, and deep. Plexiform neurofibromas (present in 25% of patients) are a variant of neurofibroma that are typically deeper, more anatomically complex, and more likely to be symptomatic. Deep plexiform neurofibromas may degenerate into malignant peripheral nerve sheath tumors. Other malignancies and tumors associated with neurofibromatosis include gliomas (especially optic pathway gliomas in 10%-15% of patients), pheochromocytomas, meningiomas, sarcomas, gastrointestinal tumors of neuroendocrine origin such as duodenal carcinoid tumors, and juvenile myelomonocytic leukemia. In addition to tumors and skin findings, patients may also have learning disabilities (30%-50%), skeletal anomalies, vasculopathies, and endocrinologic abnormalities.
The diagnosis of NF1 is made on clinical grounds, based on 2 or more of the following features:
- Six or more café au lait macules greater than 5 mm in prepubertal individuals and greater than 15 mm in diameter in postpubertal patients
- Two or more Lisch nodules (iris hamartomas) in older patients
- Sphenoid dysplasia or thinning of a long bone's cortex, with or without pseudoarthrosis
- Two or more neurofibromas of any type or a single plexiform neurofibroma
- Freckling in the axillary or inguinal region
- Optic glioma (in early childhood)
- First-degree relative with NF1 (although new mutations are frequent)
Many individuals with NF lead long and healthy lives. Overall life expectancy may be decreased by as much as 15 years secondary to complications, however.
For more information on Neurofibromatosis Type 1, see OMIM.
For more information on Neurofibromatosis Type 2, see OMIM.
Q85.01 – Neurofibromatosis, type 1
Q85.02 – Neurofibromatosis, type 2
19133005 – Neurofibromatosis syndrome
Other forms of neurofibromatosis:
- Segmental / mosaic NF1
- Watson syndrome (a subset of neurofibromatosis associated with pulmonic stenosis)
- Autosomal dominant multiple café au lait macules alone (some allelic with NF1)
- Neurofibromatosis type 2
- Schwannomatosis (disorder associated with mutation in the gene INI1)
- McCune-Albright syndrome – Premature puberty, bony abnormalities, and a few large café au lait macules with an irregular outline. In NF1, the outline of the café au lait macule is smooth.
- Genetic disorders of DNA repair or chromosomal instability
- Homozygosity for one of the genes causing hereditary nonpolyposis
- Cancer of the colon
- Noonan syndrome
- Lipomatosis (see lipoma)
- Bannayan-Riley-Ruvalcaba syndrome
- Multiple endocrine neoplasia type 1 (MEN1) and 2B (MEN2B)
Isolated neurofibromas without neurofibromatosis are also common.