Presymptomatic DNA and MRI diagnosis of neurofibromatosis 2 with mild clinical 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 with a benign course of NF2 (mild Gardner type) characterized by slowly growing vestibular schwannomas but few other manifestations. The family was thoroughly investigated with neurologic, ophthalmologic, and neuro-otologic methods including gadolinium-enhanced MRI of the head and spine and DNA linkage analysis. In the clinical analysis of 22 family members, 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 markers (CRYB2, NEFH, D22S268, and D22S280) can also be used for presymptomatic diagnosis in other NF2 families. Early detection of NF2 gene mutation carriers has become possible using linkage analysis in familial NF2. MRI screening of carriers will reveal presymptomatic vestibular schwannomas (and other CNS tumors), making early intervention possible, but an efficient treatment strategy to prevent deafness has not yet been established.