Current basic and clinical research is aimed at understanding how the genetic mutations that cause the benign tumors of NF1 also cause neurons and neural networks to form abnormally during fetal development, which later result in the learning disabilities and cognitive deficits of children with the disorder. The NINDS also encourages research to develop improved methods to diagnose the neurofibromatoses and identify factors that contribute to the wide variations of symptoms and severity of the disorders.
Ongoing NINDS-sponsored research continues to discover additional genes that appear to play a role in NF-related tumor suppression or growth. Continuing research on these genes and their proteins is beginning to reveal how this novel family of growth regulators controls tumors formation and growth. Understanding the molecular pathways and mechanisms that govern these key proteins and their activities will offer scientists exciting opportunities to design drugs that could replace the missing proteins in people who have the neurofibromatoses, and return their cell production to normal.
In the mid-1990s, research supported by the NINDS located the exact position of the NF1 gene on chromosome 17. The gene has been cloned and its structure continues to be analyzed. The NF1 gene makes a large and complex protein called neurofibromin, which is primarily active in nervous system cells as a regulator of cell division and functions as a kind of molecular brake to keep cells from over-multiplying. In addition to work on NF1, intensive efforts have led to the identification of the NF2 gene on chromosome 22. As in NF1, the NF2 gene product is a tumor-suppressor protein (called merlin or schwannomin).
The National Institute of Neurological Disorders and Stroke (NINDS), one of the National Institutes of Health (NIH), is the primary federal supporter of research on neurological diseases. The Institute sponsors basic studies aimed at understanding normal and abnormal development of the brain and nervous system, as well as clinical trials to improve the diagnosis and treatment of neurological disorders. In conjunction with the other NIH institutes, the NINDS supports research focused on finding better ways to prevent, treat, and ultimately cure the neurofibromatoses.
Clinical genetic testing can confirm the presence of a mutation in the NF1 gene. Prenatal testing for the NF1 mutation is also possible using amniocentesis or chorionic villus sampling procedures. Genetic testing for the NF2 mutation is sometimes available, but is accurate only in about 65 percent of those individuals tested. Prenatal or genetic testing for schwannomotosis currently does not exist.
There is no currently accepted medical treatment or drug for schwannomatosis, but surgical management is often effective. Pain usually subsides when tumors are removed completely, although it may recur should new tumors form. When surgery isn’t possible, ongoing monitoring and management of pain in a multidisciplinary pain clinic is advisable.
Anyone with schwannomatosis experiences some degree of pain, but the intensity varies. A small number of people have such mild pain that they are never diagnosed with the disorder. Most people have significant pain, which can be managed with medications or surgery. In some extreme cases, pain will be so severe and disabling it will keep people from working or leaving the house.
The distinguishing feature of schwannomatosis is the development of multiple schwannomas everywhere in the body except on the vestibular nerve. The dominant symptom is pain, which develops as a schwannoma enlarges, compresses nerves, or presses on adjacent tissue. Some people experience additional neurological symptoms, such as numbness, tingling, or weakness in the fingers and toes. Individuals with schwannomatosis do not have neurofibromas.
Schwannomatosis is a rare form of neurofibromatosis that is genetically and clinically distinct from NF1 and NF2. Inherited forms of the disorder account for only 15 percent of all cases. Researchers have identified a mutation of the SMARCB1/INI1 gene that is associated with the familial form of the disease but don’t fully understand what causes the intense pain that characterizes this disorder.