Wechsler Individual Achievement Test.

Objectives/Hypothesis

To perform a systematic review of GJB2-associated hearing loss to describe genotype distributions and auditory phenotype.



Data Sources

230 primary studies identified from Pubmed.



Review Methods

Pubmed was searched systematically to screen broadly for any study reporting on genotype and carrier frequencies for biallelic GJB2-associated hearing loss in defined populations around the world. Genotype and audiometric data were extracted and subjected to meta-analysis to determine genotype distributions, carrier frequencies, rates of asymmetric or progressive hearing loss, and imaging abnormalities.



Results

A total of 216 articles comprising over 43,000 hearing-loss probands were included. The prevalence of biallelic GJB2-associated hearing loss was consistent across most of the 63 countries examined, with different mutations being predominant in different countries. Common mutations were found in greater than 3% of the general population worldwide. Meta-analysis of 48 case-control studies demonstrated a two-fold higher carrier frequency among hearing-impaired individuals compared to normal-hearing controls for truncating alleles, but not V37I. Progression, asymmetry, and imaging abnormalities were present in 14% to 19% of individuals with GJB2-associated hearing loss.



Conclusion

GJB2 mutations are highly prevalent around the world. The multiple predominant mutations present in different populations attest to the importance of this gene for normal cochlear function and suggests an evolutionary heterozygote advantage. The unusually high carrier rate for truncating mutations among hearing-impaired individuals is consistent with either the presence of complementary mutations or a carrier phenotype. The significant rate of asymmetry and progression highlights the importance of diagnostic workup and close follow-up for this highly variable condition. Laryngoscope, 124:E34–E53, 2014

GJB2-associated hearing loss: systematic review of worldwide prevalence, genotype, and auditory phenotype

Since the early 1980s, audiologists have become increasingly aware of the potential effect of even mild degrees of hearing loss on the psychoeducational and psychosocial outcomes of children. This review describes some of the key research findings during the past several decades that have led us to our current thinking about unilateral and mild bilateral hearing loss in children. The first section addresses unilateral hearing loss. This is followed by a review of the literature on mild bilateral hearing loss. Specifically, the issues addressed include the significance of permanent mild degrees of hearing loss on children's psychoeducational and psychosocial development and the speech, language, and auditory characteristics of children with mild degrees of hearing loss. Finally, some recommendations regarding the direction of future research are offered. This review is followed by 2 articles summarizing the proceedings of a 2005 workshop convened by the Centers for Disease Control and Prevention (CDC), Early Hearing Detection and Intervention (EHDI) program, and the Marion Downs Hearing Center to address concerns about the underidentification of-- and professionals' apparent lack of awareness of-- permanent unilateral and minimal to mild hearing loss in children.

/pdf/unilateral-and-mild-bilateral-hearing-loss-in-children-past-2997cl2fve.pdf

Unilateral and mild bilateral hearing loss in children: past and current perspectives.

Importance Working memory training may help children with attention and learning difficulties, but robust evidence from population-level randomized controlled clinical trials is lacking. Objective To test whether a computerized adaptive working memory intervention program improves long-term academic outcomes of children 6 to 7 years of age with low working memory compared with usual classroom teaching. Design, Setting, and Participants Population-based randomized controlled clinical trial of first graders from 44 schools in Melbourne, Australia, who underwent a verbal and visuospatial working memory screening. Children were classified as having low working memory if their scores were below the 15th percentile on either the Backward Digit Recall or Mister X subtest from the Automated Working Memory Assessment, or if their scores were below the 25th percentile on both. These children were randomly assigned by an independent statistician to either an intervention or a control arm using a concealed computerized random number sequence. Researchers were blinded to group assignment at time of screening. We conducted our trial from March 1, 2012, to February 1, 2015; our final analysis was on October 30, 2015. We used intention-to-treat analyses. Intervention Cogmed working memory training, comprising 20 to 25 training sessions of 45 minutes’ duration at school. Main Outcomes and Measures Directly assessed (at 12 and 24 months) academic outcomes (reading, math, and spelling scores as primary outcomes) and working memory (also assessed at 6 months); parent-, teacher-, and child-reported behavioral and social-emotional functioning and quality of life; and intervention costs. Results Of 1723 children screened (mean [SD] age, 6.9 [0.4] years), 226 were randomized to each arm (452 total), with 90% retention at 1 year and 88% retention at 2 years; 90.3% of children in the intervention arm completed at least 20 sessions. Of the 4 short-term and working memory outcomes, 1 outcome (visuospatial short-term memory) benefited the children at 6 months (effect size, 0.43 [95% CI, 0.25-0.62]) and 12 months (effect size, 0.49 [95% CI, 0.28-0.70]), but not at 24 months. There were no benefits to any other outcomes; in fact, the math scores of the children in the intervention arm were worse at 2 years (mean difference, −3.0 [95% CI, −5.4 to −0.7]; P  = .01). Intervention costs were A$1035 per child. Conclusions and Relevance Working memory screening of children 6 to 7 years of age is feasible, and an adaptive working memory training program may temporarily improve visuospatial short-term memory. Given the loss of classroom time, cost, and lack of lasting benefit, we cannot recommend population-based delivery of Cogmed within a screening paradigm. Trial Registration anzctr.org.au Identifier:ACTRN12610000486022

https://jamanetwork.com/journals/jamapediatrics/articlepdf/2498559/poi150105.pdf

Academic Outcomes 2 Years After Working Memory Training for Children With Low Working Memory : A Randomized Clinical Trial

OBJECTIVE: The goal was to determine the prevalence and effects of slight/mild bilateral sensorineural hearing loss among children in elementary school. METHODS: A cross-sectional, cluster-sample survey of 6581 children (response: 85%; grade 1: n = 3367; grade 5: n = 3214) in 89 schools in Melbourne, Australia, was performed. Slight/mild bilateral sensorineural hearing loss was defined as a low-frequency pure-tone average across 0.5, 1, and 2 kHz and/or a high-frequency pure-tone average across 3, 4, and 6 kHz of 16 to 40 dB hearing level in the better ear, with air/bone-conduction gaps of < 10 dB. Parents reported children's health-related quality of life and behavior. Each child with slight/mild bilateral sensorineural hearing loss, matched to 2 normally hearing children (low-frequency pure-tone average and high-frequency pure-tone average of < or = 15 dB hearing level in both ears), completed standardized assessments. Whole-sample comparisons were adjusted for type of school, grade level, and gender, and matched-sample comparisons were adjusted for nonverbal IQ scores. RESULTS: Fifty-five children (0.88%) had slight/mild bilateral sensorineural hearing loss. Children with and without sensorineural hearing loss scored similarly in language (mean: 97.2 vs 99.7), reading (101.1 vs 102.8), behavior (8.4 vs 7.0), and parent- and child-reported child health-related quality of life (77.6 vs 80.0 and 76.1 vs 77.0, respectively), but phonologic short-term memory was poorer (91.0 vs 102.8) in the sensorineural hearing loss group. CONCLUSIONS: The prevalence of slight/mild bilateral sensorineural hearing loss was lower than reported in previous studies. There was no strong evidence that slight/mild bilateral sensorineural hearing loss affects adversely language, reading, behavior, or health-related quality of life in children who are otherwise healthy and of normal intelligence.

Slight/Mild Sensorineural Hearing Loss in Children

Objective To determine the benefits of a low intensity parent-toddler language promotion programme delivered to toddlers identified as slow to talk on screening in universal services.

https://www.bmj.com/content/bmj/343/bmj.d4741.full.pdf

Outcomes of population based language promotion for slow to talk toddlers at ages 2 and 3 years: Let’s Learn Language cluster randomised controlled trial

BACKGROUND: There is a lack of information on prevalence, cause and consequences of slight/mild bilateral sensorineural hearing loss (SNHL) in children. We report the first systematic genetic analysis of the GJB2 gene in a population-derived sample of children with slight/mild bilateral SNHL. METHODS: Hearing tests were conducted in 6240 Australian elementary school children in Grades 1 and 5. 55 children (0.88%) were found to have a slight/mild sensorineural hearing loss. 48 children with slight/mild sensorineural hearing loss and a matched group of 90 children with normal hearing participated in a genetic study investigating mutations in the GJB2 gene, coding for connexin 26, and the presence of the del(GJB6-D13S1830) and del(GJB6-D13S1854) deletions in the GJB6 gene, coding for connexin 30. RESULTS: Four of 48 children with slight/mild sensorineural hearing loss were homozygous for the GJB2 V37I change. The four children with homozygous V37I mutations were all of Asian background and analysis of SNPs in or near the GJB2 gene suggests that the V37I mutation arose from a single mutational event in the Asian population. DISCUSSION: Based on the prevalence of carriers of this change we conclude that V37I can be a causative mutation that is often associated with slight/mild sensorineural hearing loss. No other children in the slight/mild hearing loss group had a hearing loss related to a GJB2 mutation. One child with normal hearing was homozygous for the R127H change and we conclude that this change does not cause hearing loss. Two children of Asian background were carriers of the V37I mutation. Our data indicate that slight/mild sensorineural hearing loss due to the GJB2 V37I mutation is common in people of Asian background.

/pdf/the-contribution-of-gjb2-mutations-to-slight-or-mild-hearing-ho3u6l7ilb.pdf

The contribution of GJB2 mutations to slight or mild hearing loss in Australian elementary school children

Outcomes of population based language promotion for slow to talk toddlers at ages 2 and 3 years: Let's Learn Language cluster randomised controlled trial

Sherryn Tobin

Papers

Slight/Mild Sensorineural Hearing Loss in Children

Outcomes of population based language promotion for slow to talk toddlers at ages 2 and 3 years: Let’s Learn Language cluster randomised controlled trial

The contribution of GJB2 mutations to slight or mild hearing loss in Australian elementary school children

Outcomes of population based language promotion for slow to talk toddlers at ages 2 and 3 years: Let's Learn Language cluster randomised controlled trial

Data Resource Profile: The Victorian Childhood Hearing Impairment Longitudinal Databank (VicCHILD).