The cardinal features of neurofibromatosis are café au lait spots, axillary or inguinal freckling, cutaneous neurofibromas, and iris hamartomas (Lisch nodules). Café au lait spotsare present in more than 90% of patients who have NF1 (Fig. 186-1). They typically appear in the first few years of life and increase in number and size over time. The presence of six or more café-au-lait spots larger than 5 mm in a prepubescent child suggests the diagnosis. Lisch nodules also increase in frequency with age and are present in more than 90% of adults who have NF1.
FIGURE 186-1 Cafe au lait macules. (From Kliegman RE, Behrman RE, Jenson HB, editors: Nelson Textbook of Pediatrics, ed 19, Phila-delphia, 2007, Saunders, p 2680.)
Neurofibromas are composed of various combinations of Schwann cells, fibroblasts, mast cells, and vascular elements. Dermal neurofibromas are nearly universal and consist of discrete, small, soft lesions that lie within the dermis and epidermis and move passively with the skin. They rarely cause any symptoms, but can cause significant cosmetic concerns. Neurofibromas may also be situated within viscera or along blood vessels and peripheral nerves. Plexiform neurofibromas are large, occasionally nodular, subcutaneous lesions that lie along the major peripheral nerve trunks. They often cause symptoms including pain, weakness, and invasion of adjacent viscera, bone, or spinal cord. Sarcomatous degeneration may occur. Surgical treatment may be attempted, but results are often unsatisfactory.
Common complications are learning disability, scoliosis, seizures, and cerebral vasculature abnormalities. Other tumors that occur in NF1 are optic nerve gliomas, astrocytomas of brain and spinal cord, and malignant peripheral nerve tumors. T2-weighted magnetic resonance images (MRI) reveal hyperintense lesions (hamartomas) in the optic tracts, internal capsule, thalamus, cerebellum, and brainstem that are common and distinctive for the disease. They are benign and disappear in adulthood.
The average life expectancy of patients with NF1 may be reduced by 10 to 15 years. Malignancy is the most common cause of death. Genetic and psychological counseling are important components of care for this chronic disorder. Although it is an autosomal dominant disorder, spontaneous mutations account for 30% to 50% of cases.
Neurofibromatosis type 2 (NF2) is an autosomal-dominant disorder with an incidence of 1 in 25,000. Half the cases have no family history. The NF2 gene is a tumor suppressor gene, and disease results in neurologic, eye, and skin lesions. NF2 predisposes patients to multiple intracranial and spinal tumors, including bilateral acoustic schwannomas, schwannomas of other cranial and spinal nerves, meningiomas, and gliomas. Posterior capsular or cortical cataracts are common, and skin lesions include plaque-like lesions, subcutaneous nodules, and cutaneous schwannomas. Lisch nodules, cafe au lait spots, and axillary freckling are not features of NF2.