PRESYMPTOMATIC DNA AND MRI DIAGNOSIS OF NEUROFIBROMATOSIS-2 WITH MILDCLINICAL COURSE IN AN EXTENDED PEDIGREE

Neurofibromatosis 2 (NF2), a dominantly inherited disorder, typically manifests as bilateral vestibular schwannomas and predisposes to other nervous system tumors. In this study, we present a large pedigree wit h a benign course of NF2 (mild Gardner type) characterized by slowly g rowing vestibular schwannomas but few other manifestations. The family was thoroughly investigated with neurologic, ophthalmologic, and neur o-otologic methods including gadolinium-enhanced MRI of the head and s pine and DNA linkage analysis. In the clinical analysis of 22 family m embers, MRI was superior to neuro-otologic methods in the detection of asymptomatic tumors. Based on the DNA Linkage analyses we identified the NF2 mutation carriers with a high degree of certainty. These DNA m arkers (CRYB2, NEFH, D22S268, and D225280) can also be used for presym ptomatic diagnosis in other NF2 families. Early detection of NF2 gene mutation carriers has become possible using linkage analysis in famili al NF2. MRI screening of carriers will reveal presymptomatic vestibula r schwannomas (and other CNS tumors) making early intervention possibl e, but an efficient treatment strategy to prevent deafness has not yet been established.