NEUROFIBROMATOSIS 2 (NF2) - CLINICAL CHARACTERISTICS OF 63 AFFECTED INDIVIDUALS AND CLINICAL-EVIDENCE FOR HETEROGENEITY

To determine the spectrum of manifestations in neurofibromatosis 2 (NF 2) and to assess possible heterogeneity, we evaluated 63 affected indi viduals from 32 families. Work-up included skin and neurologic examina tions, audiometry, a complete ophthalmology examination with slit-lamp biomicroscopy of the lens and fundus, and gadolinium-enhanced MRI of the brain and, in some, of the spine. Mean age-at-onset in 58 individu als was 20.3 years; initial symptoms resulted from vestibular schwanno mas (44.4%), other CNS tumors (22.2%), skin tumors (12.7%), and ocular manifestations including cataracts and retinal hamartomas (12.7%). Fi ve asymptomatic individuals were diagnosed through screening. Vestibul ar schwannomas were documented in 62 individuals (98.4%); other findin gs included cataracts (81.0%), skin tumors (67.7%), spinal tumors (67. 4%), and meningiomas (49.2%). Usually, clinical manifestations and cou rse were similar within families but differed among families. To asses s possible heterogeneity, we assigned affected individuals to three pr oposed subtypes (representing mild, intermediate, and severe NF2) base d on age at-onset, presence or absence of CNS tumors other than vestib ular schwannomas, and presence or absence of retinal hamartomas. Compa risons among the three subtypes for many clinical parameters demonstra ted that patients in the mild subtype differed from those in the other two subtypes for most parameters, but that none of the parameters dis tinguished patients in the intermediate subtype from those in the seve re subtype. Thus, there are likely two rather than three subtypes of N F2. Classification of patients to subtype may aid in counseling about long-term prognosis and in formulating individualized guidelines for m edical surveillance. (C) 1994 Wiley-Liss, Inc.