Neurofibromatosis occurs in 1 in 2,500 to 4,000 persons. It is transmitted as an autosomal dominant trait with close to 100% penetrance. There is also a characteristically high rate (~50%) of spontaneous mutations, which may explain why only about 50% of patients have a family history of the disease. The gene for peripheral (von Recklinghausen) neurofibromatosis (NF1) is located on chromosome 17; the gene for central (bilateral acoustic) neurofibromatosis (NF2) has its locus on chromosome 22. This discussion is limited to von Recklinghausen neurofibromatosis.

DIAGNOSTIC CRITERIA

The diagnosis of von Recklinghausen neurofibromatosis in a child requires a high index of suspicion. If two or more of the criteria shown in Plate 4-20 are identified in a child, that individual can be considered to have NF1. By the age of 1 year, 70% will meet diagnostic criteria, with 97% fulfilling diagnostic criteria by the age of 8 years. With time, all manifestations of neurofibromatosis increase in number, size, and severity.

The most common musculoskeletal manifestations are spinal deformity, limb-length discrepancy, pseudarthrosis of the tibia, and problems such as pathologic fractures and hemihypertrophy of the foot, face, and hand. Despite multiple musculoskeletal manifestations of NF1, only approximately 10% of those affected will require orthopaedic intervention in their lifetime. Of those that require operations, many will require multiple procedures.

NF1 is characterized by the involvement of multiple organ systems outside the skeletal system. Neurologic, visual, and hearing problems are associated characteristics. In children, the incidence of several manifestations, such as sexual precocity, learning disorders, retarded sexual development, malignant hypertension secondary to diffuse renal artery changes, and mental retardation, is not statistically significant. The oftennoted delay of speech and motor development may signify central nervous system involvement.

CUTANEOUS LESIONS

Café-au-lait spots—the characteristic cutaneous lesions of neurofibromatosis—are present in 90% of patients (see Plate 4-20). These spots are macular and melanotic with smooth edges, in contrast to the jagged edges seen in similar lesions of fibrous dysplasia (McCune-Albright syndrome). Café-au-lait spots in NF1 have been likened to the “coast of California,” whereas lesions of fibrous dysplasia resemble the “rugged coast of Maine.”

An adult with more than six café-au-lait spots with diameters of 15 mm or greater must be presumed to have neurofibromatosis. Results of an evaluation of children younger than age 5 indicate that two or fewer café-au-lait spots occur in less than 1% of normal children and that five spots with a diameter of at least 5 mm are pathognomonic. Cutaneous neurofibroma “nodules” (fibroma molluscum), pigmented nevi, elephantiasis, and verrucous hyperplasia are other characteristic skin lesions.