Using a heteroduplex approach and direct sequencing, we have completed the screening of approximately 88% of the neurofibromatosis type 2 (NF2)-coding sequence of DNA extracted from 33 schwannomas from NF2 patients and from 29 patients with sporadic schwannomas. The extensive screening has resulted in the identification of 33 unique mutations. Similarly to other human genes, we have shown that the CpG sites are more highly mutable in the NF2 gene. The frequency, distribution, and types of mutations were shown to differ between the sporadic and familial tumors. The majority of the mutations resulted in protein truncation and were consistent with more severe phenotype, however three missense mutations were identified during this study and were all associated with milder manifestations of the disease.

Cochleosaccular dysplasia or degeneration (Scheibe degeneration) is considered the most common cause of profound congenital hearing impairment, and accounts for approximately 70% of cases 2 with hereditary deafness. A five-generation family with hereditary hearing impairment associated with cochleosaccular degeneration has recently been identified. The diagnosis of classical Scheibe degeneration was based on histopathological findings in the temporal bones of the proband, a 61-year-old profoundly deaf male. Auditory structures in the brainstem of the proband were also studied. Twenty-two members of the family were contacted for surveys and blood samples. Of these, 6 males and 2 females have hearing impairment. Complete audiological evaluation was done on 12 family members, and prior audiologic records of the proband and affected family members were available for study. Affected family members suffer a mild bilateral high-frequency hearing loss during childhood and adolescence, and progress to moderate-to-profound deafness in the second and third decades of life. The family is suitable for linkage analysis and does not map to previously reported loci harboring autosomal dominant, nonsyndromic hereditary hearing impairment genes. The genetic study of this family will be helpful in identifying the genes which, when mutated, result in Scheibe degeneration.

The presence of perilymph fistula has been difficult to determine because of the lack of efficient and reliable testing methods. The condition is suspected on the basis of history alone and confirmed by surgery. This paper details a quick, reliable procedure called the ENG fistula test, using impedance bridge for pressure change and electronystagmography to aid the establishment of nystagmus and dizziness. To evaluate this procedure, a combination of tests were performed, including Valsalva maneuver, tragal compression, and pneumatic otoscopy, which were previously considered helpful in the diagnosis of fistula. Of them, Valsalva maneuver and tragal compression proved inconclusive; pneumatic otoscopy proved to be helpful. In comparison, however, the ENG fistula test proved most valuable, with results surgically confirmed in 90.8% of cases in this series. This study involved 74 patients whose primary complaint was dizziness. Only some patients simultaneously experienced hearing lows. Included are 5 patients whose positive ENG fistula test results and 15 whose negative test results were confirmed by surgery. Selected case histories are presented.

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In 24 temporal bones from patients with otosclerosis prepared by the method of microdissection and surface preparations, otosclerotic foci could be clearly seen during removal of the otic capsule. The state of activity of each focus was estimated on the basis of its consistency and vascularity. Small anterior foci constituted the most common form of involvement of the otic capsule. All were judged to be inactive, and none of them appeared to have caused obvious sensorineural degeneration. No cases of “pure cochlear otosclerosis” were seen. Sensorineural degeneration was associated with large anterior foci which reached the upper basal turn. One specimen displayed a circumscribed sensorineural degeneration in the upper basal turn, with an almost exact correspondence between the location and extent of the cochlear lesion and the site of invasion by the otosclerotic process in the bone and endosteum bordering on scala media and scala tympani. It is postulated that a toxic factor had diffused from the focus and acted directly on the organ of Corti. When multiple foci were present they were usually poorly defined. The otosclerotic process involved the round window, with new lamellar bone formation in the scala tympani of the lower half of the basal turn. The most extensive sensorineural degeneration in the entire material was seen in this group. One specimen also had severe cochlear hydrops. In three specimens large shunts were observed to connect the otosclerotic foci with the cochlear vasculature, which was severely dilated. Where otosclerosis involved the endosteum of the scala tympani, loss of vessels was observed. One specimen with extensive active capsular otosclerosis had severe sensorineural degeneration of the vestibular system. Vestibular pathology in fenestrated ears is also described. In a specimen from a patient with no caloric reaction, numerous hair cells were present in the macular organs.

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We used computer techniques to reconstruct in three dimensions 12 vestibular nuclear complexes (VNC) from serially sectioned brains of 7 patients. Specimens were from 4 patients with vestibular disorders and 3 patients considered vestibular normal. Despite the variety of the patient’s otologic histories all the nuclei demonstrated the same shape and structural characteristics.