Headache, hydrocephalus, and tumors involving the optic pathways, meningiomas, gliomas, and malignant peripheral nerve tumors are common, even among adults, according to the survey of 158 patients by Créange and colleagues; also, pain was a common symptom in adults and often related to a malignant peripheral nerve sheath tumor.
Other abnormalities associated less consistently with type 1 (peripheral) NF include bone cysts, pathologic fractures (pseudoarthrosis), cranial bone defects with pulsating exophthalmos (sphenoid bone dysgenesis), bone hypertrophy, precocious puberty, pheochromocytoma, scoliosis, syringomyelia, nodules of abnormal glia cells in brain and spinal cord, and macrocephaly, rarely with obstructive hydrocephalus as a result of overgrowth of glial tissue around the sylvian aqueduct and fourth ventricle. Some degree of intellectual impairment is common; it was found in 40 percent of Riccardi’s series of 133 patients. But in our experience, the figure is much lower and the impairment is usually not profound. Learning difficulty, developmental disorder, and hyperactivity have been more frequent abnormalities, occurring in almost 40 percent of patients. Rosman and Pearce have ascribed developmental delay in NF to congenital malformation of the cerebral cortex (cortical dysgenesis). The incidence of seizures is about 20 times higher than that in the general population, but these tend not to be a very frequent or intractable problem.
Exceptionally, NF is associated with peroneal muscular atrophy, congenital deafness, and partial albinism (Bradley et al).
In childhood, progressive blindness is a particularly dire complication from a tumor mass composed mainly of astrocytes (optic glioma). The tumor may involve one or both optic nerves. The diagnosis comes to mind at once in a child with any of the cutaneous manifestations of NF and this tumor. Uncertainty as to its nature arises from the fact that the neuropathologist may be unable to decide between a benign hamartoma and a grade 1 astrocytoma. Progressive enlargement in a succession of MRI scans may be needed to affirm its nature.
It needs to be stated that neurofibromas of the spinal roots occur regularly in patients without NF (see Chaps. 42 and 43). Whether multiple such lesions implicate NF is not clear.
Neurofibromatosis Type 2 (Acoustic, or Central, NF)
This condition is considerably less frequent than NF1. Here there is an absence or paucity of cutaneous lesions. Progressive deafness and the demonstration by enhanced CT or MRI of bilateral acoustic neuromas afford accurate diagnosis (see Fig. 30-18). Also, an acoustic neuroma developing before age 30 years is suspect as being caused by NF2. Other cranial or spinal neurofibromas, meningioma (sometimes multiple), and glioma may be added to the syndrome of deafness or may occur prior to its emergence. Juvenile cataracts of the subcortical or capsular variety are seen in some affected patients.
Analysis for the NF2 gene is available and the genetics and affected protein (merlin or schwannomin) are discussed in “Cause and Pathogenesis” above.