Noise levels within the ear and post-nasal space in neonates in intensive care.

BACKGROUND: Noise exposure in neonatal units has long been suspected of being a cause of hearing loss associated with such units. The noise intensity to which the neonate is exposed varies with the type of ventilatory support used. Also, the post-nasal space is an enclosed cavity that is close to the inner ear and an area of turbulent and hence potentially noisy airflow. AIM: To determine noise intensities within the ear and post-nasal space in neonates on different modes of ventilatory support using probe microphones, measures previously not undertaken. METHODS: A portable instrument with a probe microphone was used for the measurements. Three groups of infants were included: (a) those receiving no respiratory support (NS); (b) those receiving conventional ventilation (CV); (c) those receiving continuous positive airways pressure (CPAP) support. RESULTS: The mean in-the-ear noise intensities (at 1 kHz) were 41.7 dB SPL (NS), 39.5 dB SPL (CV), and 55.1 dB SPL (CPAP). The noise intensities in the post-nasal space in those receiving CPAP support were higher than in the other groups, reached mean levels of up to 102 dB SPL at some frequencies, and increased with increasing flow rates. CONCLUSIONS: The most important finding is the high noise intensities in the post-nasal space of those receiving CPAP support. Given the proximity of the post-nasal space to the inner ear, enough noise could be transmitted, especially in infants receiving the higher flow rates, to cause cochlear damage and hence hearing loss. It would therefore be wise, wherever possible, to avoid using the higher flow rates.

Hearing aids versus ventilation tubes in persistent otitis media with effusion: a survey of clinical practice.

A postal survey was carried out to determine the current clinical practice amongst consultant otolaryngologists in the UK, regarding re-insertion of ventilation tubes or recommendation of hearing aids in cases of recurrence of otitis media with effusion (OME) after ventilation tube extrusion. Amongst the 319 respondents, 15 (4.70 per cent) routinely, 146 (45.77 per cent) sometimes, and 158 (49.53 per cent) either never, or very rarely, recommend hearing aids. Hearing aids and ventilation tubes were both suggested to be equally good options by some consultants but they preferred surgery for a number of reasons. There were inconsistencies in practice and some of the reasons for re-inserting ventilation tubes are not evidence-based. A hearing aid is a non-invasive option and this survey shows a need for a randomized control trial of hearing aids and ventilation tubes in the management of persistent and recurrent OME.

Evaluation of the use of a questionnaire to detect hearing loss in Kenyan pre-school children.

In developing countries, there is a lack of trained personnel and testing equipment to facilitate the early detection of hearing impairment in children. A questionnaire offers a low cost option and the value of this for detecting hearing impairment in pre-school children was determined in several districts in Kenya. The questionnaire was completed by either teachers, parents/carers or community nurses. The children were subsequently tested using pure tone audiometry and visual examination of the ear by ENT Clinical Officers, who were not given prior access to the results of the questionnaire. A total of 757 (88%) questionnaires were completed. Of the 735 children, who could be tested using pure tone audiometry, four were found to have a unilateral hearing impairment and one was detected by the questionnaire. A total of 13 children had a bilateral hearing impairment >40 dB HL. All were detected using the questionnaire. There were eight males and five females with ages ranging from 4.2 to 6.9 years, mean age 5.7 years and median age 5.8 years. Eight had a sensorineural hearing impairment and two a mixed hearing impairment. Three of the children with a sensorineural hearing loss had a family history of hearing impairment. No question detected all children with a hearing impairment and some questions were more discerning than others. There was 100% sensitivity for the questionnaire when a hearing loss of >40 dB was considered, but specificity was lower at 75%. Negative predictive value was 100%, but the positive predictive value was low, 6.75%. It was concluded that a questionnaire of this nature could be usefully applied at Primary Health Care level for detecting hearing impairment at the pre-school stage. There would be need for services available for diagnosis, treatment and habilitation before a screening programme was introduced.

Congenital non-syndromal sensorineural hearing impairment due to connexin 26 gene mutations--molecular and audiological findings.

We screened DNA from 72 sibships and 138 sporadically affected individuals with congenital non-syndromal sensorineural hearing impairment (NSSNHI) for mutations in the 26 (CX26) gene. A total of 20 (27.8%) of the sibships and 11 (7.9%) of the sporadically affected individuals were homozygous or compound heterozygotes for CX26 mutations. A total of 11 (17.2%) of 64 individuals with severe and 30 (30%) of 100 with profound NSSNHI compared to eight (8.7%) of 92 persons with moderate and none (0%) of 19 individuals with mild hearing impairment were homozygous or compound heterozygotes for CX26 mutations (chi2 test, 3 df, P = 0.000). CX26 mutation status bad no effect on the symmetry of the hearing impairment or configuration of the audiogram. In addition, serial audiograms showed no evidence of progression of the hearing impairment or differences in the severity of the hearing impairment in affected siblings in persons whether or not due to CX26 mutations. Sporadically affected individuals with congenital NSSNHI should be routinely tested for mutations in CX26, especially if the hearing impairment is severe or profound in severity, since identification of a mutation in CX26 allows use of Mendelian recurrence risks.

Otoacoustic emissions in 28 young adults exposed to amplified music.

Popular concern about widespread damage to the hearing from exposure to amplified music continues, although there has been little firm evidence of permanent effects in casual listeners. Measurement of transient evoked otoacoustic emissions (TEOAEs) provides a sensitive technique for testing outer hair cell (OHC) function, and was used in this study of 28 young adults aged 18-25 years, whose only significant source of noise exposure was loud music, to look for evidence of poorer cochlear function in those of greater exposure; they provided 27 right ears and 27 left ears suitable for measurement of TEOAE strength. Estimates of subjects' total noise dose were obtained from self-reports of the duration and intensity of their exposure to music and other sources of noise. Ears with greater exposure to loud music showed significantly weaker TEOAEs than less exposed ears in response to a 4 kHz tone burst, or in response to a saturating (82 dBSPL) click if the response was treated with a high-frequency bandpass filter (2-4 kHz) (p<0.05). Differences between more exposed and less exposed groups of ears were most marked in the 2 kHz half-octave band for right ears, and in the 2.8 kHz half-octave band for left ears. A hypothesis is proposed that weakness in TEOAEs as a result of exposure to loud music is seen first in the 2 kHz region of the emission spectrum, and later at higher frequencies; and that for a given amount of exposure, TEOAE weakness (or OHC damage) is more advanced in left ears than in right.

Evaluation of the use of a questionnaire to detect hearing loss in babies in China.

A questionnaire was used to screen hearing of 1020 babies 6-8 months in China. All babies failing the questionnaire and 10% of those who passed were tested using auditory brainstem audiometry (ABR). Babies with unilateral or bilateral hearing thresholds 30 dBnHL or more were investigated to determine the cause of the hearing impairment. Sixty-seven failing the questionnaire were tested and 23 were confirmed to have a hearing loss, 20 with bilateral hearing impairment. The causes were: 13 otitis media with effusion (OME), one hypoxia, one genetic and five unknown. One child with an OME related hearing loss passed the screen. The sensitivity of the questionnaire was estimated to be 70%, specificity 96%.

Waardenburg syndrome.

Auditory-pigmentary syndromes are caused by physical absence of melanocytes from the skin, hair, eyes, or the stria vascularis of the cochlea. Dominantly inherited examples with patchy depigmentation are usually labelled Waardenburg syndrome (WS). Type I WS, characterised by dystopia canthorum, is caused by loss of function mutations in the PAX3 gene. Type III WS (Klein-Waardenburg syndrome, with abnormalities of the arms) is an extreme presentation of type I; some but not all patients are homozygotes. Type IV WS (Shah-Waardenburg syndrome with Hirschsprung disease) can be caused by mutations in the genes for endothelin-3 or one of its receptors, EDNRB. Type II WS is a heterogeneous group, about 15% of whom are heterozygous for mutations in the MITF (microphthalmia associated transcription factor) gene. All these forms show marked variability even within families, and at present it is not possible to predict the severity, even when a mutation is detected. Characterising the genes is helping to unravel important developmental pathways in the neural crest and its derivatives.

Distortion product emissions in normal-hearing and low-frequency hearing loss carriers of genes for Waardenburg's syndrome.

Eight patients with Waardenburg's syndrome (WS) with normal hearing and 3 additional patients exhibiting a low-frequency hearing loss were tested for the level of the acoustic distortion product 2f1-f2 by means of the Otodynamics Distortion Product Analyser (ILO92). Wide notches in distortion product otoacoustic emissions (DPOAEs) between 1,000 and 3,000 Hz were found in 7 (12 ears, 87.5%) examined patients with normal audiograms, which was a significantly higher rate than that found in the control group (10%). The 3 patients with low-frequency hearing loss a gave a consistent pattern in audiometric configuration shown by both pure tone audiograms and DPOAEs. It is concluded from these initial results that DPOAEs may be a useful approach to identifying subclinical pathologic aberrations in the inner ear in WS patients, and may be a predictor of low-frequency sensorineural hearing loss.

A clinical, genetic and audiological study of patients and families with unilateral vestibular schwannomas. II. Audiological findings in 93 patients with unilateral vestibular schwannomas.

Nine-three patients with histologically or radiologically confirmed unilateral vestibular schwannomas were recruited. Audiological testing for retrocochlear pathology was undertaken. Patients' hospital records were examined for previous audiological and radiological results. The audiometric configuration was designated as one of the following: normal, sloping, low frequency, peak, trough or flat. A sloping sensorineural audiometric configuration was present in 68 per cent of cases. No significant correlation was found between tumour size and average pure tone threshold 500 Hz to 4000 Hz, optimum discrimination score or interaural differences for wave V. Ninety-one per cent of cases had abnormalities on auditory evoked potential; 92 per cent of cases showed abnormalities on stapedial reflex testing. The limitations of audiological testing in the investigation of patients with suspected unilateral vestibular schwannomas are discussed. A protocol for the investigation of such patients is presented.

A clinical, genetic and audiological study of patients and families with unilateral vestibular schwannomas. I. Clinical features of neurofibromatosis in patients with unilateral vestibular schwannomas.

Ninety-three patients with unilateral vestibular schwannomas were examined in a clinical, genetic and audiological study, to determine whether they had features associated with neurofibromatosis Type 1 or neurofibromatosis Type 2. In 91 families, one patient only was found to be affected with a unilateral vestibular schwannoma. Patients did have a few café-au-lait macules, but fewer than six in number. None of the patients satisfied the cutaneous diagnostic criteria for neurofibromatosis Type 1. Neither Lisch nodules nor presenile posterior subcapsular lenticular opacities or cortical opacities were a feature. Five patients with unilateral vestibular schwannomas are described where the clinical findings raised the possibility of neurofibromatosis Type 2. It is suggested that certain individuals with unilateral vestibular schwannomas are at risk of developing neurofibromatosis Type 2. Furthermore, the possibility of neurofibromatosis Type 2 should be considered if more than one individual in a family is found to be affected with a unilateral vestibular schwannoma.

Linkage studies of non-syndromic recessive deafness (NSRD) in a family originating from the Mirpur region of Pakistan maps DFNB1 centromeric to D13S175.

Autosomal recessive non-syndromal hearing impairment (NSRD) is genetically heterogeneous. Five loci have been identified to date which map to chromosomes 13 (DFNB1), 11 (DFNB2), 17 (DFNB3), 7 (DFNB4) and 14 (DFBN5). We report definite linkage of NSRD to the locus DFNB1 in a single family of 27 families studied of Pakistani origin. Haplotype analysis of markers in the pericentromeric region of chromosome 13q revealed a recombination event which maps DFNB1 proximal to the marker D13S175 and in the vicinity of D13S143.

The mutational spectrum in Waardenburg syndrome.

One hundred and thirty-four families or individuals with auditory-pigmentary syndromes such as Waardenburg syndrome (WS) or probable neurocristopathies were screened for mutations in the PAX3 and MITF genes. PAX3 mutations were found in 20/25 families with definite Type 1 WS and 1/2 with Type 3 WS, but in none of 23 with definite Type 2 WS or 36 with other neurocristopathies. The PAX3 mutations included substitutions of conserved amino acids in the paired domain or the homeodomain, splice-site mutations, nonsense mutations and frame-shifting insertions or deletions. No phenotype-genotype correlations were noted within WS1 families. With MITF, mutations likely to affect protein function were found in seven families, five of which had definite Type 2 WS. We conclude that Type 1 and Type 3 WS are allelic and are normally caused by loss of function mutations in PAX3; that Type 2 WS is heterogeneous, with about 20% of cases caused by mutations in MITF, and that individuals with auditory, pigmentary or neural crest syndromes which do not fit stringent definitions of Waardenburg syndrome are unlikely to have mutations in either the PAX3 or MITF genes. The molecular pathology of MITF/microphthalmia mutations appears to be different in humans and mice, with gene dosage having more significant effects in humans than in the mouse.

Waardenburg syndrome type II: phenotypic findings and diagnostic criteria.

The Waardenburg syndrome (WS) consists of at least two distinct autosomal dominant hereditary disorders. WS Type I has been mapped to the distal part of chromosome 2q and the gene identified as PAX3. Other gene(s) are responsible for WS Type II. Mapping WS Type II requires accurate diagnosis within affected families. To establish diagnostic criteria for WS Type II, 81 individuals from 21 families with Type II WS were personally studied, and compared with 60 personally studied patients from 8 families with Type I and 253 cases of WS (Type I or II) from the literature. Sensorineural hearing loss (77%) and heterochromia iridum (47%) were the two most important diagnostic indicators for WS Type II. Both were more common in Type II than in Type I. Other clinical manifestations, such as white forelock and skin patches, were more frequent in Type I. We estimate the frequency of phenotypic traits and propose diagnostic criteria for WS Type II. In practice, a diagnosis of WS Type II can be made with confidence given a family history of congenital hearing loss and pigmentary disorders, where individuals have been accurately measured for ocular distances to exclude dystopia canthorum.

Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene.

Waardenburg syndrome type 2 (WS2) is a dominantly inherited syndrome of hearing loss and pigmentary disturbances. We recently mapped a WS2 gene to chromosome 3p12.3-p14.1 and proposed as a candidate gene MITF, the human homologue of the mouse microphthalmia (mi) gene. This encodes a putative basic-helix-loop-helix-leucine zipper transcription factor expressed in adult skin and in embryonic retina, otic vesicle and hair follicles. Mice carrying mi mutations show reduced pigmentation of the eyes and coat, and with some alleles, microphthalmia, hearing loss, osteopetrosis and mast cell defects. Here we show that affected individuals in two WS2 families have mutations affecting splice sites in the MITF gene.

A gene for Waardenburg syndrome type 2 maps close to the human homologue of the microphthalmia gene at chromosome 3p12-p14.1.

Waardenburg syndrome (WS), an autosomal dominant syndrome of hearing loss and pigmentary disturbances, comprises at least two separate conditions. WS type 1 is normally caused by mutations in PAX3 located at chromosome 2q35 and is distinguished clinically by minor facial malformations. We have now located a gene for WS type 2. Two families show linkage to a group of microsatellite markers located on chromosome 3p12-p14.1. D3S1261 gave a maximum lod score of 6.5 at zero recombination in one large Type 2 family. In a second, smaller family the adjacent marker D3S1210 gave a lod of 2.05 at zero recombination. Interestingly, the human homologue (MITF) of the mouse microphthalmia gene, a good candidate at the phenotypic level, has recently been mapped to 3p12.3-p14.4.

PAX3 gene structure and mutations: close analogies between Waardenburg syndrome and the Splotch mouse.

The human PAX3 gene contains a paired box and a paired-type homeobox, and is believed to play a role in pattern formation in the embryo. We describe the exon-intron structure of the homeobox-containing part of PAX3, complementing earlier descriptions of the 5' part of the gene. Mutations in PAX3 have been described in patients with Type 1 Waardenburg syndrome, who have hearing loss and pigmentary abnormalities, while Splotch mice have mutations in the homologous mouse Pax-3 gene. We describe a series of patients who have previously unidentified PAX3 mutations. These include a chromosomal deletion, a splice-site mutation and an amino acid substitution which closely correspond to the molecular changes seen in the Splotch-retarded, Splotch and Splotch-delayed mouse mutants respectively. These mutations confirm that Waardenburg syndrome is produced by gene dosage effects and show that the phenotypic differences between Splotch mice and humans with Waardenburg syndrome are caused by differences in genetic background rather than different primary effects of the mutations.

Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2.

Waardenburg syndrome (WS) is a combination of deafness and pigmentary disturbances, normally inherited as an autosomal dominant trait. The pathology involves neural crest derivatives, but WS is heterogeneous clinically and genetically. Some type I WS families show linkage with markers on distal 2q and in three cases the disease has been attributed to mutations in the PAX3 gene. PAX3 encodes a paired domain, a highly conserved octapeptide and probably also a paired-type homeodomain. Here we describe a further three PAX3 mutations which cause WS; one alters the octapeptide motif plus the presumed homeodomain; a second alters all three elements and the third alters the paired box alone. The latter occurs in a family with probable type 2 WS, a clinical variant usually considered not to be allelic with type 1 WS.

A clinical, genetic and audiological study of patients and families with bilateral acoustic neurofibromatosis.

The neurofibromatoses consist of at least two distinct autosomal dominant hereditary disorders. Neurofibromatosis type 1 (NF1) is due to a lesion on chromosome 17q. Neurofibromatosis type 2 (NF2) is caused by a defect on chromosome 22q. The hallmark of NF2 is the development, in the second and third decades, of bilateral acoustic neuromas. NF1 is characterized by the appearance of café-au-lait spots and neurofibromas in addition to iris hamartomas, or Lisch nodules, of the eye, during the first and second decades. Ten families were personally studied. A total of 16 members were found to be affected with NF2. A protocol for evaluation and review of subjects and relatives of NF2 families is proposed. A team approach, coordinating the expertise of multiple specialties is recommended.