Unilateral vestibular schwannoma with other neurofibromatosis Type 2-related tumors: clinical and molecular study of a unique phenotype

Object. Although the manifestations of neurofibromatosis Type 2 (NF2) vary, the hallmark is bilateral vestibular schwannomas (VSs). The authors studied the clinical course and genetic basis of unilateral VSs associated with other NF2-related tumors. Methods. Forty-four adults presenting with unilateral VSs and other NF2-related tumors were identified. A comprehensive review of patient records and cranial imaging was conducted. Molecular analysis of the NF2 locus was performed in available tumors and paired blood specimens. Patient age at symptomatic onset ranged from 11 to 63 years (mean 32 years). Twenty-two patients (50%) presented with eighth cranial nerve dysfunction. Twenty-six presented with multiple lesions. Thirty-eight harbored other intracranial tumors and 27 had spinal tumors, with most lesions situated ipsilateral to the VS. No patient had a relative with NF2, although two of 63 offspring had isolated NF2-related findings. A contralateral VS developed in four patients 3 to 46 years after the symptomatic onset of a unilateral VS, and two of these patients experienced rapid progression to total deafness. Results of a Kaplan-Meier analysis identified actuarial chances of developing contralateral VS: 2.9% (3-17 years after the VS symptomatic onset of unilateral VS), 11% (18-24 years), and 28.8% (25-40 years). Mosaicism for the NF2 gene mutation was proven in eight patients. Conclusions. The authors describe the clinical features of this unique phenotype-unilateral VS with other NF2-related tumors. Persons with this phenotype should undergo evaluation and monitoring similar to that conducted in patients with NF2, and the possibility of aggressive contralateral VS fort-nation should be considered in their treatment. Molecular genetic analysis is best performed using resected tumor specimens and will enable future studies to determine the genetic risks of individuals with mosaicism.