Adult aqueductal stenosis presenting with fluctuating hearing loss and vertigo. Report of two cases.

Two cases of aqueductal stenosis presenting with fluctuating hearing loss, tinnitus, and vertigo are presented. Audiovestibulometric assessment of both cases disclosed the characteristic pattern of disorder of the membranous inner ear. Non-tumoral aqueductal stenosis was demonstrated by computerized tomography in one case and by positive contrast ventriculography in the other. Shunting procedures of the cerebrospinal fluid resulted in resolution of inner ear dysfunction in both patients.

The site of the hearing loss in Refsum's disease.

Refsum's disease is a disorder of lipid metabolism with pigmentary retinopathy, demyelinating neuropathy, ataxia, and hearing loss. Previous histological studies have located the site of hearing impairment in the inner ear, but it has never been confirmed audiologicaly in the literature. In this reported case of Refsum's disease, despite hearing loss and absence of response in ABR, robust otoacoustic emissions were measured. Together with these and other audiological findings, we conclude that our case might be the first reported case of Refsum's disease with auditory neuropathy. The site of the hearing abnormality in Refsum's disease may be 'post-outer hair cells' in some cases as in the current case. Because of their limited benefits and risk of noise-induced damage to outer hair cells, the use of hearing aids before otoacoustic emission measurements should be considered cautiously in Refsum's disease.

The place of conservation surgery for T3 laryngeal carcinomas with fixation.

Although the traditional surgical treatment of T3 laryngeal carcinomas is total laryngectomy, we have obtained favorable survival results for selected cases with partial laryngectomy, as exemplified in the literature. Extending the indications up to ultimate limits by partial, but radical surgical techniques is the recent trend in the world, for the conservation surgery of laryngeal cancers. The primary treatment of T3 laryngeal cancers, instead of irradiation, should be surgical and, for select cases partial laryngectomy, depending on laryngeal embryological development and lymphatic drainage, may be carried out. We have performed partial laryngectomy with elective or therapeutic and radical or modified radical neck dissection for 43 T3 laryngeal carcinomas at the Department of Otolaryngology, Istanbul Medical Faculty, University of Istanbul in the years 1978-1991 and obtained 2, 3, and 5 years of survival rates, which are 89, 79.4, and 73%, respectively.

Audiometric manifestations of Waardenburg's syndrome.

We studied 23 patients (from 11 families) who had Waardenburg's syndrome. Patients were evaluated by conventional audiometric methods and by distortion-product otoacoustic emissions to determine the penetrance and the degree and type of hearing loss. Twelve of the patients had the type I form of the syndrome and 11 had type II. Overall, we found hearing loss in 19 of the 23 patients (83%); hearing loss affected nine type I patients (75%) and 10 type II patients (91%). Five type I patients (42%) and eight type II patients (73%) had a hearing loss of > 100 dB. Bilateral symmetrical hearing loss was the most common type of loss, as it was seen in six of the type I patients (50%) and eight of the type II patients (73%). At lower frequencies, distortion-product otoacoustic emission amplitudes were found to be significantly above the noise floor in five of the 11 patients whose hearing thresholds were 60 dB HL or worse by click auditory brainstem response testing. These findings led us to conclude that it is necessary to use otoacoustic emissions in patients with Waardenburg's syndrome in order to provide optimum fitting of hearing aids, especially in children.

Frequencies of gap- and tight-junction mutations in Turkish families with autosomal-recessive non-syndromic hearing loss.

Mutations in genes encoding gap- and tight-junction proteins have been shown to cause distinct forms of hearing loss. We have now determined the GJB2[connexin 26 (Cx26)] mutation spectrum in 60 index patients from mostly large Turkish families with autosomal-recessive inherited non-syndromic sensorineural hearing loss (NSSHL). GJB2 mutations were found in 31.7% of the families, and the GJB2-35delG mutation accounted for 73.6% of all GJB2 mutations. The carrier frequency of GJB2-35delG in the normal Turkish population was found to be 1.17% (five in 429). In addition to the described W24X, 233delC, 120delE and R127H mutations, we also identified a novel mutation, Q80R, in the GJB2 gene. Interestingly, the Q80R allele was inherited on the same haplotype as V27I and E114G polymorphisms. As little is known about the mutation frequencies of most other recently identified gap- and tight-junction genes as a cause for hearing loss, we further screened our patients for mutations in GJB3 (Cx31), GJA1 (Cx43), DeltaGJB6-D13S1830 (Cx30) and the gene encoding the tight-junction protein, claudin 14 (CLDN14). Several novel polymorphisms, but no disease-associated mutations, were identified in the CLND14 and GJA1 genes, and we were unable to detect the DeltaGJB6-D13S1830 deletion. A novel putative mutation, P223T, was found in the GJB3 gene in heterozygous form in a family with two affected children. Our data shows that the frequency of GJB2 mutations in Turkish patients with autosomal-recessive NSSHL and the carrier rate of the GJB2-35delG mutation in the Turkish population, is much lower than described for other Mediterranean countries. Furthermore, mutations in other gap- and tight-junction proteins are not a frequent cause of hearing loss in Turkey.

The novel R75Q mutation in the GJB2 gene causes autosomal dominant hearing loss and palmoplantar keratoderma in a Turkish family.

Dominant mutations in the GJB2 gene encoding connexin 26 (Cx26) can cause non-syndromic hearing impairment alone or in association with palmoplantar keratoderma (PPK). We have identified the novel G224A (R75Q) mutation in the GJB2 gene in a four-generation family from Turkey with autosomal dominant inherited hearing impairment and PPK. The age of onset and progression of hearing loss were found to be variable among affected family members, but all of them had more severe impairment at higher hearing frequencies. Interestingly, the novel R75Q mutation affects the same amino acid residue as described recently in a small family (R75W) with profound prelingual hearing loss and PPK. However, the R75W mutation was also observed in a control individual without PPK and unknown hearing status. Therefore, the nature of the R75W mutation remains ambiguous. Our molecular findings provide further evidence for the importance of the conserved R75 in Cx26 for the physiological function of the inner ear and the epidermal cells of the skin.