Evaluation of auditory development in infants and toddlers who received cochlear implants under the age of 24 months with the LittlEARS) Auditory Questionnaire.

BACKGROUND AND AIMS: Newborn hearing screening and early intervention for congenital hearing loss have created a need for tools assessing the hearing development of very young children. A multidisciplinary evaluation of children's development is now becoming standard in clinical practice, though not many reliable diagnostic instruments exist. For this reason, the LittlEARS Auditory Questionnaire (LEAQ) was created to assess the auditory skills of a growing population of infants and toddlers who receive hearing instruments. The LEAQ relies on parent report, which has been shown to be a reliable way of assessing child development. Results with this tool in a group of children who received very early cochlear implantation are presented. METHODS: The LEAQ is the first module of the LittlEARS comprehensive test battery for children under the age of two who have normal hearing (NH), cochlear implants (CIs) or hearing aids (HAs). The LEAQ is a parent questionnaire comprised of 35 "yes/no" questions which can be completed by parents in less than 10 min. Sixty-three children who received unilateral CIs at a young age were assessed longitudinally and their performance was compared to that of a NH group. RESULTS: All CI children reached the maximum possible score on the LEAQ on average by 22 months of hearing age, i.e. 38 months of chronological age. In comparison, the NH group reached the maximum score by 24 months of age demonstrating that auditory skills of CI children often develop quicker than those of NH children. In the two comparison groups of children aged (a) younger and older than 12 months, and (b) between 6-9 and 21-24 months at first fitting, the early implanted children reached the highest scores faster than the later implanted children. Furthermore, three children with additional needs were tested. They showed slower growth over time but also received benefits from early implantation. CONCLUSIONS: The LEAQ is a quick and effective tool for assessing auditory skills of very young children with or without hearing loss. In our study, the auditory skills of children with CI progressed very quickly after implantation and were comparable with those of NH peers.

Phenotypic variability of patients homozygous for the GJB2 mutation 35delG cannot be explained by the influence of one major modifier gene.

Hereditary hearing loss (HL) is a very heterogeneous trait, with 46 gene identifications for non-syndromic HL. Mutations in GJB2 cause up to half of all cases of severe-to-profound congenital autosomal recessive non-syndromic HL, with 35delG being the most frequent mutation in Caucasians. Although a genotype-phenotype correlation has been established for most GJB2 genotypes, the HL of 35delG homozygous patients is mild to profound. We hypothesise that this phenotypic variability is at least partly caused by the influence of modifier genes. By performing a whole-genome association (WGA) study on 35delG homozygotes, we sought to identify modifier genes. The association study was performed by comparing the genotypes of mild/moderate cases and profound cases. The first analysis included a pooling-based WGA study of a first set of 255 samples by using both the Illumina 550K and Affymetrix 500K chips. This analysis resulted in a ranking of all analysed single-nucleotide polymorphisms (SNPs) according to their P-values. The top 250 most significantly associated SNPs were genotyped individually in the same sample set. All 192 SNPs that still had significant P-values were genotyped in a second independent set of 297 samples for replication. The significant P-values were replicated in nine SNPs, with combined P-values between 3 x 10(-3) and 1 x 10(-4). This study suggests that the phenotypic variability in 35delG homozygous patients cannot be explained by the effect of one major modifier gene. Significantly associated SNPs may reflect a small modifying effect on the phenotype. Increasing the power of the study will be of greatest importance to confirm these results.

Universal newborn hearing screening and postnatal hearing loss.

OBJECTIVE: The goal of this study was to determine the percentage of children who have a postnatal permanent childhood hearing impairment (PCHI) and the percentage thereof who have risk indicators for a postnatal hearing loss. METHODS: Data were drawn retrospectively from the clinical charts of children who had bilateral PCHI (>40 dB hearing level, better ear, unaided) and had undergone universal newborn hearing screening (UNHS) between 1995 and 2000 in various Austrian hospitals. A hearing loss was recognized as postnatal when a child passed UNHS but was later found to have a hearing impairment. The presence of risk indicators, as suggested by the Year 2000 Statement of the American Joint Committee on Infant Hearing (JCIH), was assessed by reviewing the children's clinical charts. RESULTS: Of a total of 105 children with bilateral PCHI, 23 (22%) showed postnatal impairment. After correction of this number for underascertainment, postnatal impairment was estimated to account for 25% of all bilateral PCHI at age 9 years. Risk indicators were found in 17 children but did not fully correspond to those proposed by the JCIH. The risk factors found were a family history of hearing loss (3 children), meningitis (2), craniofacial malformation (2), persistent pulmonary hypertension (1), congenital cytomegaly infection (1), extracorporeal membrane oxygenation (1), recurrent otitis media with effusion (1), and, in addition to the JCIH list, ototoxic therapy (5), and birth before 33rd gestational week (2) (1 child had a combination of the last 2). Six children showed no risk indicators for the postnatal hearing loss. CONCLUSIONS: Our findings suggest that approximately 25% of bilateral childhood hearing loss is postnatal, which supports the leading role of UNHS in detecting PCHI. Provisions for also identifying postnatal cases nevertheless are justified. Because in some of these children no risk indicators are detectable and in others the hearing deterioration starts after age 3 years, audiologic monitoring of at-risk children up to this age may not be sufficient. Additional methods, such as hearing screening at nursery schools or schools, are recommended.

Ten-year outcome of newborn hearing screening in Austria.

OBJECTIVE: Current health care standards recommend that congenital hearing loss be confirmed before age three months and intervened for before age six months. This study evaluated to what extent the Austrian universal neonatal hearing screening (UNHS) program achieves this goal. The Austrian UNHS program is a hospital-based, two-stage screen based on transient oto-acoustic emissions, as promoted in 1995 in a position paper of the Austrian ENT Society. METHODS: Retrospective chart review and data analysis. All Austrian institutions engaged in the diagnosis and treatment of childhood hearing loss were requested to provide their data on children with permanent congenital sensorineural hearing impairment registered since 1990. Children who had undergone hearing screening, were compared to those who had not. Main outcome measures were age at confirmation of and age at intervention for the hearing loss. In each group, the percentage of children, whose hearing loss was confirmed by age three months, and intervened for by age six months, was determined. RESULTS: Data from 321 hearing-impaired children were useable. Of these children, 167 were screened and 154 were not. At age three months, a hearing loss was diagnosed in 35% of screened children, but in only 2% of unscreened. These percentages rose to 69% and 6%, respectively, at age six months and to 81% and 12%, respectively, at age one year. Intervention mostly started within less than one month after diagnosis. At age six months, 61% of screened children, but only 4% of unscreened children, had undergone intervention. CONCLUSIONS: Hearing screening enormously increases the number of early-detected children. However, in quite a few screened children hearing loss is neither confirmed within three months after birth, nor intervened for within six months after birth. Reasons for the delay must be paid attention in order to warrant that UNHS can be as effective as possible.

GJB2 mutations and degree of hearing loss: a multicenter study.

Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (P<.0001). The HI of 48 different genotypes was less severe than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mild-to-moderate HI (median 25-40 dB). Two genotypes--35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)--had significantly more-severe HI than that of 35delG homozygotes.

[Evaluation of the Austrian Newborn Hearing Screening Program]. / Zehn Jahre Neugeborenen-Hörscreening in Osterreich. Eine Evaluierung.

BACKGROUND: Universal Neonatal Hearing Screening (UNHS) has been gradually implemented since the mid-nineties in Austrian maternity wards and neonatal intensive care units. This study evaluated the effect of UNHS on reducing age at identification as well as age of intervention for children with congenital and perinatal sensorineural hearing impairment. METHODS: This was a retrospective analysis of clinical data of 394 Austrian children diagnosed with an at least mild degree (> 20 dB hearing level) of permanent sensorineural hearing loss. Age at identification and age at intervention were compared between children who underwent UNHS ('with UNHS') and those who did not undergo UNHS ('without UNHS'). RESULTS: The median of age of identification was 37.6 months in children without UNHS, and 3.9 months in children with UNHS. By six months of age, 69% of hearing-impaired children who underwent UNHS, were identified but only 6% of those without UNHS. At one year, the corresponding percentages are 80% and 12%, respectively. In children without UNHS, the degree of hearing loss was the most predictive factor of age at identification (median of age at diagnosis for profound hearing loss: 15 months; severe: 26 months; moderate: 52 months; mild: 73 months). In children with UNHS, age of identification was unrelated to degree of hearing loss (medians between 3.7 and 4.4 months). In the majority of children intervention began within one month after diagnosis, regardless of whether or not the child was identified by UNHS. DISCUSSION: UNHS greatly increases the proportion of children whose hearing impairment is diagnosed before six months of age. However, in some 20% of children, hearing impairment was diagnosed later than one year of age, despite having failed the screening. Additionally, data from this study suggest that about 15% of childhood hearing losses manifest themselves after the hearing screening period. Efforts are thus required for the early detection of these children as well.

The 342-kb deletion in GJB6 is not present in patients with non-syndromic hearing loss from Austria.

Recently, a 342-kb deletion involving GJB6 was associated with autosomal-recessive non-syndromic hearing loss (NSHL) and in combination with a GJB2 mutation with digenic NSHL. This deletion was the second most common mutation causing prelingual NSHL in Spain, and was frequently observed in patients from France and Israel. We screened 393 patients with NSHL being negative or heterozygous for GJB2 mutations for this GJB6 deletion using a multiplex PCR. Most patients were of Austrian (84.2%), and the other patients were of Turkish, Serbian, and Bosnian origin. None of these patients was carrying the deletion in GJB6 indicating that the occurrence of this deletion is restricted to certain populations.

Progressive hearing loss, and recurrent sudden sensorineural hearing loss associated with GJB2 mutations--phenotypic spectrum and frequencies of GJB2 mutations in Austria.

Mutations of GJB2 (encoding connexin 26) are the most common cause of hearing loss (HL) in different populations, and a broad spectrum of GJB2 mutations has been identified. We screened 204 consecutive patients with non-syndromic sensorineural hearing loss for GJB2 mutations. Causative GJB2mutations were identified in 31 (15.2%) patients, and two common mutations, c.35delG and L90P (c.269T>C), accounted for 72.1% and 9.8% of GJB2 disease alleles. In four additional patients (2.0%) only one recessive GJB2 mutation was identified, making genetic counselling difficult. No genotype-phenotype correlation was established. We found, however, that homozygotes for truncating mutations were more likely to have a more severe degree of HL compared with other genotypes. Moreover, we showed by co-segregation studies that L90P is a GJB2 disease allele, and that compound heterozygotes for L90P and any recessive mutation share a mild to moderate phenotype. GJB2-associated HL was linked with progressive HL or with recurrent sudden sensorineural hearing loss (SSNHL) in three of 15 cases being analysed retrospectively. We extended the phenotypic spectrum of GJB2-related disease and recommend GJB2 mutation screening also in cases of progressive HL, and recurrent SSNHL. In addition, a carrier frequency of 1/110 (0.9%) for the most common Caucasian mutation in this gene, c.35delG, was determined in 1,212 blood donors from West-Austria, supporting the prevailing hypothesis of a Mediterranean founder mutation. Based on population and patient data, an overall GJB2 mutation carrier frequency of 1.3% was estimated for West-Austria.