von Recklinghausen's Neurofibromatosis Health Article

Definition

Von Recklinghausen's neurofibromatosis is also called von Recklinghausen disease or simply neurofibromatosis (NF). It is an automsomal dominant hereditary disorder. NF is the most common neurological disorder caused by a single gene. Patients develop multiple soft tumors (neurofibromas) and very often skin spots (freckling AND café au lait). The tumors occur under the skin and throughout the nervous system.

Description

There are three types of neurofibromatosis. The two main types of neurofibromatosis are Neurofibromatosis 1 (NF1) and Neurofibromatosis 2 (NF2). NF1 is more common than NF2. NF1 affects approximately 1 in 2, 000 to 1 in 5, 000 births worldwide. NF2 affects 1 in 35, 000 to 1 in 40, 000 births worldwide. Recently, schwannomatosis has been recognized as a rare form of NF. Since NF is the most common neurological disorder, NF is more prevalent than the number of people affected by cystic fibrosis, hereditary muscular dystrophy, Huntington's disease, and Tay Sachs combined. In addition to skin and nervous system tumors and skin freckling, NF can lead to disfigurement, blindness, deafness, skeletal abnormalities, loss of limbs, malignancies, and learning disabilities. The degree a person is affected with a form of neurofibromatosis may vary greatly between patients.

Causes and symptoms

A defective gene causes NF1 and NF2. NF1 is due to a defect on chromosome 17. NF2 results from a defect on chromosome 22. Both neurofibromatosis disorders are inherited in an autosomal dominant fashion. In an autosomal dominant disease, one copy of a defective gene will cause the disease. However, family pattern of NF is only evident for about 50% to 70% of all NF cases. The remaining cases of NF are due to a spontaneous mutation (a change in a person's gene rather than a mutation inherited from a parent). As with an inherited mutated gene, a person with a spontaneously mutated gene has a 50% chance of passing the spontaneously mutated gene to any offspring.

NF1 has a number of possible symptoms:

• Five or more light brown skin spots (café au lait spots, a French term meaning "coffee with milk"). The skin spots measure more than 0.2 inches (5 millimeters) in diameter in patients under the age of puberty or more than 0.6 inches (15 millimeters) in diameter across in adults and children over the age of puberty. Nearly all NF1 patients display café au lait spots.
• Multiple freckles in the armpit or groin area.
• Ninety percent of patients with NF1 have tiny tumors in the iris (colored area of the eye) called Lisch nodules (iris nevi).
• Two or more Neurofibromas. Neurofibromas are soft tumors and are the hallmark of NF1. Neurofibromas occur under the skin, often located along nerves or within the gastrointestinal tract. Neurofibromas are small and rubbery, and the skin overlying them may be somewhat purple in color.
• Skeletal deformities, such as a twisted spine (scoliosis), curved spine (humpback), or bowed legs.
• Tumors along the optic nerve, which cause vision disturbance in about 20% of patients.
• The presence of NF1 in a patient's parent, child, or sibling.

There are very high rates of speech impairment, learning disabilities, and attention deficit disorder in children with NF1. Other complications include the development of a seizure disorder, or the abnormal accumulation of fluid within the brain (hydrocephalus). A number of cancers are more common in patients with NF1. These include a variety of types of malignant brain tumors, as well as leukemia, and cancerous tumors of certain muscles (rhabdomyosarcoma), the adrenal glands (pheochromocytoma), or the kidneys (Wilms' tumor). Symptoms are often visible at birth or during infancy, and almost always by the time a child is about 10 years old.

In contrast to patients with NF1, patients with NF2 have few, if any, café au lait spots or tumors under the skin. Patients with NF2 most commonly have tumors (schwannomas) on the eighth cranial nerve (one of 12 pairs of nerves that enter or emerge from the brain), and occasionally on other nerves. The location of the schwann cell derived tumors determines the effect on the body. The characteristic symptoms of NF2 include dysfunction in hearing, ringing in the ears (tinnitus), and body balance. The common characteristic symptoms of NF2 are due to tumors along the acoustic and vestibular branches of the eighth cranial nerve. Tumors that occur on neighboring nervous system structures may cause weakness of the muscles of the face, headache, dizziness, numbness, and weakness in an arm or leg. Cloudy areas on the lens of the eye (called cataracts) frequently develop at an early age. As in NF1, the chance of brain tumors developing is unusually high. Symptoms of NF2 may not begin until after puberty.

Multiple schwannomas on cranial, spinal, and peripheral nerves characterize schwannomatosis. People with schwannomatosis usually have greater problems with pain than with neurological disability. The first symptom of schwannomatosis is usually pain in any part of the body without any source. It can be several years before a tumor is found. About 1/3 of patients with schwannomatosis have tumors in a single part of the body, such as an arm, leg or segment of spine. People with schwannomatosis do not develop vestibular tumors, any other kinds of tumors (such as meningiomas, ependymomas, or astrocytomas), do not go deaf, and do not have learning disabilities.