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.
The diagnosis of NF1 is made on clinical grounds, based on 2 or more of the following features if not better explained by an alternate diagnosis:
- Six or more café au lait macules greater than 5 mm in diameter in prepubertal patients and greater than 15 mm in diameter in postpubertal patients
- Two or more Lisch nodules (iris hamartomas)
- An osseous lesion such as sphenoid dysplasia or thinning of a long bone's cortex, with or without pseudoarthrosis
- At least 2 neurofibromas of any type or a single plexiform neurofibroma
- Freckling in the axillary or inguinal region
- Optic glioma (in early childhood)
- A first-degree relative with NF1
Other malignancies and tumors associated with NF1 include gliomas (especially optic pathway gliomas, occurring 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 (including heart disease), and endocrinologic abnormalities.
Neurofibromatosis type 2 (also known as bilateral acoustic neurofibromatosis, central neurofibromatosis, or NF2) is an inherited, autosomal dominant genetic disorder that affects approximately 1 in 33 000 individuals. Patients with NF2 present primarily with vestibular schwannomas (schwannomas of the eighth cranial nerve), which are frequently bilateral. Hearing loss may also be present. NF2, which is 10 times less common than NF1, is associated with mutation of a different tumor suppressor gene that is located on chromosome 22 and codes for a protein called merlin. Patients have fewer café au lait macules than those with NF1, and they do not form Lisch nodules in the iris.
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 NF1, see OMIM.
For more information on NF2, 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 – Skin schwannomas may be an early but rare sign of NF2.
- Schwannomatosis – A 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 – Constitutional mismatch repair-deficiency syndrome is an inherited autosomal recessive condition that can present with axillary freckling and café au lait macules but is associated with early onset hematologic malignancies.
- Hereditary nonpolyposis colorectal cancer (HNPCC)
- Noonan syndrome
- Lipomatosis (see lipoma)
- Bannayan-Riley-Ruvalcaba syndrome
- Multiple endocrine neoplasia type 1 (MEN1) and type 2B (MEN2B)