Semen analysis in the Usher syndrome type 2A.

Semen analysis in patients with Usher syndrome suggested that defective connecting cilia axonemes may be involved in the irreversible, progressive loss of photoreceptors in Usher's syndrome. In the framework of clinical genetic research into Usher syndrome, a pilot study was set up to test these findings. The semen of 6 Usher 2A patients was analysed. The fertility status of the study group of Usher 2A patients was evaluated, including semen analysis, supplemented by electron microscopic examination of the spermatozoa. Except for a significantly increased pH value, no abnormalities were found in the functional semen analysis, whereas electron microscopy revealed microtubular tail abnormalities. The latter finding was of little relevance, however, in view of the normal motility of the spermatozoa observed in these patients. There were no fertility problems in our group of Usher 2A patients, nor have any been mentioned in Usher patients in general. Earlier study findings were not supported by our data.

Hearing impairment related to age in Usher syndrome types 1B and 2A.

OBJECTIVE: To evaluate hearing impairment in 2 common genetic subtypes of Usher syndrome, USH1B and USH2A. DESIGN: Cross-sectional analysis of hearing threshold related to age in patients with genotypes determined by linkage and mutation analysis. SETTING: Otolaryngology department, university referral center. PATIENTS: Nineteen patients with USH1B and 27 with USH2A were examined. All participants were living in the Netherlands and Belgium. MAIN OUTCOME MEASURE: Pure tone audiometry of the best ear at last visit. RESULTS: The patients with USH1B had residual hearing without age dependence, with minimum thresholds of 80, 95, and 120 dB at 0.25, 0.5, and 1 to 2 kHz, respectively. Mean thresholds of patients with USH2A were about 45 to 55 dB better than these minimum values. Distinctive audiographic features of patients with USH2A were maximum hearing thresholds of 70, 80, and 100 dB at 0.25, 0.5, and 1 kHz, respectively, only at younger than 40 years. Progression of hearing impairment in USH2A was 0.7 dB/y on average for 0.25 to 4 kHz and could not be explained by presbyacusis alone. CONCLUSIONS: The USH1B and USH2A can be easily distinguished by hearing impairment at younger than 40 years at the low frequencies. Hearing impairment in our patients with USH2A could be characterized as progressive.

Recurrent therapy resistant mastoiditis by Mycobacterium cheilonae abscessus, a nontuberculous mycobacterium.

A rare case of recurrent mastoiditis is described with abscess formation caused by a nontuberculous mycobacterium (NTM) Mycobacterium chelonae abscessus. The exceptionally slow wound healing after repeated surgical debridement was striking. A literature study showed that in contrast with NTM infections of other parts of the body, infections of the middle ear were most commonly seen in immunocompetent children. If a case of chronic unilateral otitis media shows insufficient response to antibiotic therapy and surgical debridement, mycobacterial infection should be considered. The case described below illustrates the importance of histopathological and microbiological investigations.

Stable and progressive hearing loss in type 2A Usher's syndrome.

Audiograms were traced or additionally performed on 23 Usher's syndrome patients in 10 Dutch multi-affected families, all linked to chromosome 1q (USH2A locus). Serial audiograms, available in 13 patients, were used for a regression analysis of binaural pure tone average on age (follow-up, 9 to 32 years) to test for "significant progression," ie, a significant regression coefficient, here called the "annual threshold increase" (ATI, expressed in decibels per year). A significant ATI (> 1 dB/y) was observed in 3 patients. Analysis of variance of ATI demonstrated significant heterogeneity; hearing loss was either stable or progressive. This implies a significant clinical heterogeneity. A similar analysis performed on our progressive USH2A cases and "type III" cases previously reported by others (ATI of 1 to 5 dB/y), some of which were recently linked to chromosome 3q (USH3 locus), failed to show any significant heterogeneity in the progression of hearing loss.

Genetic heterogeneity of Usher syndrome type II in a Dutch population.

The Usher syndromes are a group of autosomal recessive disorders characterised by retinitis pigmentosa (RP) with congenital, stable (non-progressive) sensorineural hearing loss. Profound deafness, RP, and no vestibular responses are features of Usher type I, whereas moderate to severe hearing loss and RP with normal vestibular function describe Usher type II. The gene responsible for most cases of Usher II, USH2a, is on chromosome 1q41; at least one other Usher II gene (as yet unlinked) is known to exist. Usher III presents with a progressive hearing loss that can mimic the audiometric profile seen in Usher II. A gene causing Usher III in a group of Finnish families, USH3, resides on chromosome 3q. Since the phenotypes for Usher II and III overlap, it is important to determine how frequently Usher IIa, Usher IIb, and Usher III occur in a clinical population of non-Usher I patients. DNA was collected from 29 Dutch families and genotyped with six DNA markers known to flank the USH2a gene closely, and with five markers that flank USH3. Results of haplotype and linkage analysis were consistent with linkage to the USH2a locus in 26 of these 29 Dutch families. Three families displayed no linkage to 1q41 markers, and one of these three families appeared unlinked to 3q markers as well; current haplotypes of the other two families are inconclusive for linkage with the USH3 locus without further genotyping. While an A test for heterogeneity of USH2a was statistically significant, no convincing evidence of linkage to USH3 was found in this Dutch sample. Consequently, the frequency of the unlinked variety of Usher IIa (Usher IIb) in The Netherlands was estimated as 0.104. To determine if marker alleles could be used to differentiate Usher type IIa from Usher IIb, parental chromosomes of the 26 Usher IIa families were analysed for significant non-random association of specific alleles from flanking loci with USH2a, but no linkage disequilibrium was observed in this Dutch population.

Ophthalmologic findings in Usher syndrome type 2A.

Thirty-seven patients, comprising 24 familial cases and 13 isolated patients with Usher syndrome type II (USH2), underwent ophthalmologic examination. Based on the degree of hearing loss, normal vestibular function, and gene-linkage analysis, familial cases were assumed to have USH2A. An analysis of genetic heterogeneity failed to reveal the presence of a second locus in the Dutch population. Although the patients appear to belong to a genetically homogeneous group, remarkable ophthalmologic variability was found. Corrected visual acuity decreased with age and remarkable differences in visual acuity were found within one family. Fundoscopic findings were classified as type A if attenuated vessels and bone corpuscles in all quadrants were found or as type B if findings other than these were found. The prevalence of type A significantly increased with age.

Clinical findings in obligate carriers of type I Usher syndrome.

Seventeen obligate carriers from nine families with autosomal recessive Usher syndrome type I underwent otological, audiological, vestibular, and ophthalmological examination in order to identify possible manifestations of heterozygosity. Linkage studies were performed and six families showed linkage to chromosome region 11q13.5 while 3 families have so far failed to show linkage to the candidate regions. Eight obligate carriers had an abnormal pure-tone audiogram. Two different audiometric patterns could be distinguished when hearing loss was corrected for age and sex. Four carriers (24%) had significant sensorineural hearing loss (SNHL) which increased at higher frequencies. The other 13 carriers had SNHL of about 10 dB at 0.25 and 0.5 kHz, but less at higher frequencies. Vestibular findings were generally normal. Electro-oculography demonstrated a significant lower mean light peak/dark trough ratio in Usher type I carriers compared to normal control individuals. The methods used in this study were found not to be specific enough to clinically identify carriers of Usher type I syndrome. Nevertheless it is remarkable that a number of obligate carriers showed significant audiological and ophthalmological abnormalities.

Usher syndrome. A temporal bone report.

The bilateral temporal bones of a deceased 84-year-old man who had been suffering from Usher syndrome were examined using light microscopy. Histopathologic examination disclosed degeneration of the organ of Corti that was most profound in the basal turn, degeneration of cochlear neurons in all of the turns, and severe loss of spiral ganglia in both cochleas. Endolymphatic hydrops of unknown cause and a functionally unimportant pit malformation in the macular utricle were observed in the right cochlea. We compared the aforementioned findings with temporal bone reports cited in the literature.

The Usher syndrome type 2A: clinical findings in obligate carriers.

Ten obligate carriers of Usher syndrome type 2A from 5 different families with 2 affected persons all underwent audiologic, vestibular and ophthalmologic examinations. They had a sensorineural hearing loss which was in excess of that expected for their age at all of the frequencies (0.25-8 kHz) tested, however, only a 10 dB (average) excess in hearing loss at 0.25-0.5 kHz proved to be significant. The speech discrimination scores obtained conformed with the hearing thresholds. Tympanometry, acoustic reflex and brain stem auditory-evoked potential findings were generally normal. Some vestibular abnormalities were found in a minority of the carrier sample, but not beyond the level of false positivity. Ophthalmologic findings were essentially normal, although in 5 carriers there was a subnormal electrooculography (EOG). These findings are not sufficient specific for carrier detection.

Gene mapping of Usher syndrome type IIa: localization of the gene to a 2.1-cM segment on chromosome 1q41.

Usher syndrome type II is associated with hearing loss and retinitis pigmentosa but not with any vestibular problems. It is known to be genetically heterogeneous, and one locus (termed USH2A) has been linked to chromosome 1q41. In an effort to refine the localization of USH2A, the genetic map of the region between and adjacent to the marker loci previously recognized as flanking USH2A (D1S70 and PPOL) is updated. Analysis of marker data on 68 Usher II families places the USH2A gene into a 2.1-cM region between the markers D1S237 and D1S229. The gene for transforming growth factor beta 2 (TGFB2) and the gene for the homeodomain box (HLX1) are both eliminated as candidates for USH2A, by virtue of their localization outside these flanking markers. The earlier finding of genetic heterogeneity was confirmed in six new families, and the proportion of unlinked Usher II families is estimated at 12.5%. The placement of the USH2A gene into this region will aid in the physical mapping and isolation of the gene itself.

Validity of tympanometry in the diagnosis of middle ear effusion.

A group of 266 children (515 ears), ranging in age from 5 months to 11 years, was studied. These children were candidates for the insertion of ventilation tubes, or adenoidectomy and/or tonsillectomy with myringotomy. Before surgery, tympanometry was performed. The surgical and tympanometric findings were compared afterwards. Two different tympanometers were used (GSI-27A and TYMP-85TT). This study showed a comparable validity of these two tympanometers. The sensitivity and specificity of tympanometry in the age group of 5 months to 2 years did not show a significant difference from that in the age group of 2-12 years. Otoscopy has limited value for the diagnosis of middle ear effusion in this age group.

The electrooculogram in heterozygote carriers of Usher syndrome, retinitis pigmentosa, neuronal ceroid lipofuscinosis, senior syndrome and choroideremia.

Electrooculographic studies were performed in 77 carriers of tapetoretinal dystrophies: Usher syndrome (20), retinitis pigmentosa (32), neuronal ceroid lipofuscinosis (6), Senior syndrome (2), and choroideremia (17). The carriers were matched for sex and age with normal controls. In carriers of Usher syndrome the EOG Lp/Dt ratio was significantly lowered with 30% of the recordings having a subnormal value. There was a trend in carriers of retinitis pigmentosa to a subnormal EOG. In contrast to previous studies there was no decrease in the EOG Lp/Dt ratio in carriers of neuronal ceroid lipofuscinosis. Two carriers of Senior's syndrome had a normal EOG. Carriers of choroideremia did not differ significantly from normal controls; however, the Lp/Dt ratio decreased with increasing age. An abnormal EOG may be indicative of the carrier state in relatives of patients with tapetoretinal dystrophies.

Colour vision in retinitis pigmentosa. Influence of cystoid macular edema.

In retinitis pigmentosa patients the effect of cystoid macular edema on colour vision was studied. The occurrence of cystoid macular edema decreases with increasing colour vision defect. The mutual proportion of the main types of colour vision defects remains stable until visual acuity has dropped to 0.5; at lower VA levels the number of red-green defects increases. Neither the finding of a blue-yellow colour vision defect in FM100 Hue testing nor the appearance of anomaloscopic pseudoprotanomaly is influenced by cystoid macular edema. The authors conclude that cystoid macular edema in retinitis pigmentosa patients mainly affects visual acuity and not colour vision. They also noted a familial occurrence of cystoid macular edema.

Long-term follow-up of chronic therapy resistant purulent rhinitis in children.

Forty children diagnosed as having chronic purulent rhinitis unresponsive to medical and surgical management were studied. After a mean follow-up of six years and nine months the condition resolved spontaneously in 95% of the children, usually after reaching the age of 7 years.

Long-term follow-up of chronic maxillary sinusitis in children.

In 26 children, aged between 3 and 7 years, the course of therapy-resistant chronic maxillary sinusitis over a mean period of 6 years and 3 months, was analysed. The results showed that spontaneous cure had occurred in 24 of the 26 children, on average after they reached the age of 7 years. The chronic character of upper respiratory tract infections in young children is difficult to explain.