Neurofibromatosis

Arm lesions (top) and "café-au-lait" spots in neurofibromatosis.

Signs and Symptoms: Neurofibromatosis (NF­1) describes a variety of related syndromes characterized by neuroectodermal tumors arising within multiple organs. The term Von Recklinghausen's Neurofibro-matosis recognizes Friedrich Daniel Von Reckling-hausen, who first reported the constellation of findings in 1882.

The diagnostic criteria for neurofibromatosis requires at least two of the these seven systemic signs:

• Café-au-lait spots. These small brown patches on the skin are composed of epidermal melanocytes with giant pigment granules. They increase in size and number through the third decade, but decrease in number later in life
• Axillary and inguinal freckling.
• Lisch nodules of the iris. Melanocytic hamartomas appear as light brown nodules on the iris stroma in the second or third decade of life
• Neurofibromas. These benign tumors consisting predominately of Schwann cells and fibroblasts involving the skin, peripheral nerves, blood vessels and viscera appear in all patients by age 16.
• Plexiform neurofibromas. These ill-defined, soft subcutaneous swellings are usually evident at birth resulting from the diffuse thickening of nerve trunks located in the orbital or temporal region of the face.
• Optic nerve gliomas. Such benign, nonprogressive tumors have the potential to enlarge rapidly, causing proptosis and visual consequences.
• Family history of distinctive osseous lesions.

These tissue changes may produce optic neuropathy or compromise the visual pathway.

Pathophysiology: This inherited disorder is a disease of the neural crest, a transient embryonic structure composed of cells which migrate to various body parts to form neuronal, neural-supportive, pigmentary, endocrine or other tissues.

Researchers are studying the precise disease mechanisms. Significant arrays of tissues which develop from neural crest derivatives make it impossible to tie the origin of Von Recklinghausen's neurofibromatosis to a single chemical, immunologic or cellular marker.

Management: The individual course of neurofibromatosis is unpredictable, and management is difficult. There are no specific treatments, although some elements of the disease process are treatable.

Children with this syndrome are susceptible to neurological complications and should undergo neuroimaging of the brain and orbit. T-2 weighted magnetic resonance imaging (MRI) can detect both intraorbital and intracranial optic nerve gliomas. Visual evoked potential (VEP) is useful for evaluating optic nerve function. Pattern visual evoked response (VER) is useful for assessing chiasmal involvement.

Clinical Pearl:

• Genetic counseling and early detection of treatable conditions or complications are vitally important.