Neurofibromatosis is an autosomal dominant disorder that causes tumors to develop along the course of peripheral nerves and that occasionally results in marked soft-tissue or bone deformities. Diagnosis is clinical. There is no specific treatment, but tumors can be removed surgically.

Neurofibromatosis has 2 types. Type 1 (von Recklinghausen's disease) is most prevalent, causing neurologic, cutaneous, and sometimes soft-tissue or bone manifestations. Type 2 accounts for 10% of cases, manifesting primarily as congenital bilateral acoustic neuromas. The gene for type I is located on band 17q11.2, and that for type II is located on band 22q11.

Neurofibromas (benign tumors consisting of Schwann cells and neural fibroblasts) may be peripheral or central.

Peripheral neurofibromas can develop anywhere along the course of peripheral nerves. Most appear during adolescence. There are 4 forms:

• Cutaneous neurofibromas are soft and fleshy.
• Subcutaneous neurofibromas are firm and nodular.
• Nodular plexiform neurofibromas may involve spinal nerve roots, typically growing through an intervertebral foramen to cause intraspinal and extraspinal masses (dumbbell tumor). The intraspinal part may compress the spinal cord.
• Diffuse plexiform neurofibromas (subcutaneous nodules or amorphous overgrowth of underlying bone or Schwann cells) can be disfiguring and may cause deficits distal to the neurofibroma. These neurofibromas can become malignant.

Central (cranial nerve) neurofibromas have 2 forms:

• Optic gliomas: These may cause progressive blindness. They may occur in both types 1 and 2.
• Acoustic neuromas (vestibular schwannomas): These may cause dizziness, ataxia, deafness, and tinnitus. They occur in type 2.

Symptoms and Signs

Type 1

Most patients are asymptomatic. Some present with neurologic symptoms or bone deformities. In > 90%, characteristic skin lesions are apparent at birth or develop during infancy. Lesions are medium-brown (café-au-lait), freckle-like macules, distributed most commonly over the trunk, pelvis, and flexor creases of elbows and knees. During late childhood, flesh-colored cutaneous tumors of various sizes and shapes appear, ranging in number from several to thousands. Rarely, plexiform neurofibromas develop, causing an irregularly thickened, distorted structure with grotesque deformities.

Neurofibromatosis (Café-au-Lait Spots)

Neurofibromatosis (Neurofibromas)

Neurofibromatosis (Skeletal Anomalies)

Neurofibromatosis (Lisch Nodules)

Neurologic symptoms vary, depending on location and number of neurofibromas. Bone abnormalities include

• Fibrous dysplasia
• Subperiosteal bone cysts
• Vertebral scalloping
• Scoliosis
• Thinning of the long-bone cortex
• Pseudarthrosis
• Absence of the greater wing of the sphenoid bone (posterior orbital wall), with consequent pulsating exophthalmos

An optic glioma and Lisch nodules (iris hamartomas) occur in some patients. Changes in arterial walls may lead to Moyamoya disease or intracranial artery aneurysms. Some children have learning problems and slightly larger heads.

Type 2

Bilateral acoustic neuromas develop and become symptomatic during childhood or early adulthood. They cause hearing loss, unsteadiness, and sometimes headache or facial weakness. Bilateral 8th cranial (vestibulocochlear) nerve masses may be present. Family members may have gliomas, meningiomas, or schwannomas.

Diagnosis

• Clinical evaluation
• CT or MRI

Most patients with type 1 are identified during routine examination, examination for cosmetic complaints, or evaluation of a positive family history. Diagnosis is clinical (see Table 1: Neurocutaneous Syndromes: Diagnosing Neurofibromatosis). CT or MRI is done in patients with neurologic symptoms or signs on presentation and in those with other examination findings that suggest neurofibromatosis. Neuroimaging may detect 8th cranial nerve masses in type 2; MRI may show focal density changes in type 1.

Genetic testing exists but is not routinely available.

Table 1
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Diagnosing Neurofibromatosis Type Criteria 1 ≥ 2 of the following must be present: ≥ 6 café-au-lait macules with a diameter at the widest point of > 5 mm in prepubertal patients and > 15 mm in postpubertal patients ≥ 2 neurofibromas of any type or 1 plexiform neurofibroma Freckling in the axillary or inguinal region Optic glioma ≥ 2 Lisch nodules (iris hamartomas) A distinctive osseous lesion (eg, sphenoid dysplasia, thinning of long-bone cortex), with or without pseudarthrosis A parent, sibling, or child with diagnosed type 1 neurofibromatosis 2 1 of the following must be present: Bilateral 8th nerve masses seen with CT or MRI A parent, sibling, or child with type 2 neurofibromatosis and either a unilateral 8th nerve mass or any 2 of the following: Neurofibroma, meningioma, glioma, schwannoma, or juvenile posterior subcapsular lenticular opacity Adapted from Martuza RL, Eldredge R: Neurofibromatosis 2 (bilateral acoustic neurofibromatosis). Reprinted by permission of The New England Journal of Medicine 318:684–688, 1988.

Treatment

• Possibly surgery or irradiation

No general treatment is available. Neurofibromas that cause severe symptoms may require surgical removal or irradiation, although surgery may obliterate function of the involved nerve.

Genetic counseling is advisable. If either parent has neurofibromatosis, risk to subsequent offspring is 50%; if neither has it, risk for subsequent children is unclear because new mutations are common.

Last full review/revision March 2009 by Margaret C. McBride, MD