Neurofibromatosis is a genetic disorder involving an abnormality in tumor suppression with an inborn propensity for developing neurofibromas and a predisposition for certain malignancies. The presentation of the disease can be quite variable. The incidence is about 1 per 3000 people. The neurofibromatosis gene is quite large and therefore prone to a relatively high spontaneous mutation rate, approximately 1 per 10,000. The genetic abnormality has been mapped to chromosome 17 and has an autosomal dominant inheritance with variable expressivity and nearly complete penetrance. The genetics of variable expressivity explain the various clinical presentations of neurofibromatosis.
The criteria for diagnosing neurofibromatosis Type I include having 2 or more of the following clinical findings:
- six or more café au lait spots (1.5 cm or larger)
- 2 or more neurofibromas or 1 or more plexiform neurofibromas
- axillary freckling
- optic glioma
- 2 or more Lisch nodules
- Sphenoid bone dysplasia
- A first-degree relative with NF-1
There are a various findings associated with neurofibromatosis Type 1. Tumors of the central nervous system may develop, such as optic gliomas (15%). Some patients have growth or hormone problems. Less common associations include problems involving the heart, adrenal glands, or kidneys. A pheochromocytoma, a tumor involving the adrenal gland, has been associated with NF-1 (approximately 0.5-5%) and may lead to hypertension.(1) Pheochromocytomas are important for patients undergoing general anesthesia. The kidneys may be involved with renal artery stenosis, which can lead to elevated blood pressure. The aspects of hypertension tend to occur later in life. Children with neurofibromatosis Type 1 should be evaluated by a pediatric ophthalmologist annually. Patients with neurofibromatosis often require a multi-disciplinary approach.
Neurofibromatosis Type 2 is much less common than NF-1. The genetic defect is located on chromosome 22. The disease is characterized by acoustic neuromas, meningiomas, gliomas, and occassional posterior subcapsular cataracts. Retinal hamartomas may also occur with neurofibromatosis Type 2.
Additional information is located at the following links:
National Institute of Neurological Disorders and Stroke
Sources: 1. VON RECKLINGHAUSEN'S DISEASE AND PHEOCHROMOCYTOMAS. Journal of Urology. 162(5):1582, November 1999. Walther, McClellan M.; Herring, Judi; Enquist, Erik; Keiser, Harry R.; Linehan, W. Marston