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, mildto-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 (). The HI of 48 different genotypes was less severe P ! .0001 than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mildto-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.

Newborns with confirmed hearing loss should have Cx26 testing. Cx26 testing will help define a group in which approximately 60% will have profound or severe-profound hearing loss and require aggressive language intervention (many of these patients will be candidates for cochlear implants).

Mutations in OTOF cause both profound hearing loss and a type of hearing loss where otoacoustic emissions are spared called auditory neuropathy.

Purpose Usher syndrome is a major cause of genetic deafblindness. The hearing loss is usually congenital and the retinitis pigmentosa is progressive and first noticed in early childhood to the middle teenage years. Its frequency may be underestimated. Newly developed molecular technologies can detect the underlying gene mutation of this disorder early in life providing estimation of its prevalence in at risk pediatric populations and laying a foundation for its incorporation as an adjunct to newborn hearing screening programs. Methods A total of 133 children from two deaf and hard of hearing pediatric populations were genotyped first for GJB2/6 and, if negative, then for Usher syndrome. Children were scored as positive if the test revealed ≥1 pathogenic mutations in any Usher gene. Results Fifteen children carried pathogenic mutations in one of the Usher genes; the number of deaf and hard of hearing children carrying Usher syndrome mutations was 15/133 (11.3%). The population prevalence was estimated to be 1/6000. Conclusion Usher syndrome is more prevalent than has been reported prior to the genome project era. Early diagnosis of Usher syndrome has important positive implications for childhood safety, educational planning, genetic counseling, and treatment. The results demonstrate that DNA testing for Usher syndrome is feasible and may be a useful addition to newborn hearing screening programs.

Objectives/Hypothesis Compare the accuracy of wideband acoustic transfer functions (WATFs) measured in the ear canal at ambient pressure to methods currently recommended by clinical guidelines for predicting middle-ear effusion (MEE). Study Design Cross-sectional validating diagnostic study among young children with and without MEE to investigate the ability of WATFs to predict MEE. Methods WATF measures were obtained in a MEE group of 44 children (53 ears, mean age 1.9 years) scheduled for middle-ear ventilation tube placement and a normal age-matched control group of 44 children (59 ears, mean age 1.8 years) with normal pneumatic otoscopic findings and no history of ear disease or middle-ear surgery. An otolaryngologist judged whether MEE was present or absent and rated tympanic-membrane (TM) mobility via pneumatic otoscopy. A likelihood-ratio classifier reduced WATF data (absorbance, admittance magnitude and phase) from 0.25 to 8 kHz to a single predictor of MEE status. Absorbance was compared to pneumatic otoscopy classifications of tympanic membrane (TM) mobility. Results Absorbance was reduced in ears with MEE compared to ears from the control group. Absorbance and admittance magnitude were the best single WATF predictors of MEE, but a predictor combining absorbance, admittance magnitude and phase was the most accurate. Absorbance varied systematically with TM mobility based on data from pneumatic otoscopy. Conclusions Results showed that absorbance is sensitive to middle-ear stiffness and MEE, and WATF predictions of MEE in young children are as accurate as that reported for methods recommended by the clinical guidelines.