GJB2 mutations and additional disabilities in a pediatric cochlear implant population

BACKGROUND: Children with severe to profound sensorineural hearing loss due to GJB2 mutations have often been deemed good cochlear implant candidates. Studies on children with GJB2 mutations and cochlear implants have typically excluded children with additional disabilities. OBJECTIVE: To investigate the presence of additional disabilities among children with and without GJB2 mutations in a cochlear implant population. METHODS: A retrospective chart review was performed of children with non-syndromic sensorineural hearing loss (SNHL) who received a cochlear implant between 1993 and 2004. RESULTS: Among 108 children within the cochlear implant database; 46 patients met the inclusion criteria of idiopathic non-syndromic hearing loss. Sixteen children had GJB2 mutations, 12 were GJB2 negative, and 17 did not receive GJB2 testing but had no other identifiable etiology or risk factor contributing to hearing loss. The proportion of children with additional disabilities that would affect either pre-operative assessments or post-operative results in the GJB2 positive group was 44% compared to 33% of children in the GJB2 negative. Additional disabilities were present in 41% of the children who did not receive GJB2 testing. The disabilities in the GJB2 positive group included specific learning disability, apraxia, epileptiform aphasia, attention deficit disorder, global developmental delay, and gross motor delay. The GJB2 negative and those children not receiving GJB2 testing had motor delays, language delay, autism, specific learning disability, and attention deficit disorder. The proportion of children with at least 6 months CI use who relied on oral communication was 62% in the GJB2 positive group, 66% in the GJB2 negative group, and 38% in the untested group. A majority of the genetic alleles were 35delG (81%) and 10 of 16 (63%) patients with GJB2 mutations were homozygous 35delG. The rate of developmental diagnoses was similar in patients with homozygous GJB2 compared to compound heterozygous genotypes. CONCLUSIONS: The presence of biallelic GJB2 mutations does not rule out non-hearing related disorders that can have an effect on speech, language and learning. Forty-four percent of children with GJB2 mutations had other conditions that could directly affect pre-implant evaluation and post-implant performance. This rate is similar to the reported prevalence among the overall population of children with hearing loss. All children should have a comprehensive evaluation of development and behavior regardless of the etiology of hearing loss.     

Relationship between transducer type and low-frequency hearing loss for patients with ventilation tubes

OBJECTIVE: To determine the relationship between the type of transducer used to perform pure-tone audiometry and the appearance of low-frequency hearing loss at 250Hz and 500Hz for patients with ventilation tubes. METHODS: Air conduction thresholds at 250Hz and 500Hz were measured using Telephonics TDH-49 supra-aural headphones and EARTONE 3-A insert earphones for patients with normal ears (N=16) and patients with ventilation tubes (N=114). Tympanometry was performed on each patient prior to audiometric testing. Audiometric test results obtained in normal ears were compared to results for patients with ventilation tubes. For analysis, the ventilation tube patients were separated into two groups, representative of ventilation tube type. RESULTS: Audiometric results obtained using the two transducer types at 250Hz and 500Hz revealed significant differences in threshold for patients with ventilation tubes. Thresholds obtained using insert earphones were generally worse than thresholds obtained using supra-aural headphones for this group. On average, difference in threshold was 14.15dB worse with insert earphones at 250Hz and 9.75dB worse with insert earphones at 500Hz for patients with Sheehy tubes. Average difference in threshold for patients with Donaldson tubes was 13.93dB worse with insert earphones at 250Hz and 8.93dB worse with insert earphones at 500Hz. In addition, thresholds were more variable for patients with ventilation tubes than normal ears at 500Hz. There were no significant differences in threshold for normal ears using both transducers. CONCLUSIONS: When performing pure-tone audiometry, choice of transducer can influence the accurate identification of a low-frequency hearing loss in patients with ventilation tubes. Low-frequency thresholds were generally worse using insert-style earphones to test subjects with tubes, resulting in the apparent identification of a hearing loss. However, with supra-aural headphones, no low-frequency hearing loss existed. There were no significant differences in threshold values using either transducer in normal ears.     

The influence of mutations in the SLC26A4 gene on the temporal bone in a population with enlarged vestibular aqueduct

OBJECTIVE: To correlate genetic and audiometric findings with a detailed radiologic analysis of the temporal bone in patients with enlarged vestibular aqueduct (EVA) to ascertain the contribution of SLC26A4 gene mutations to this phenotype. DESIGN: A retrospective review of patients with EVA identified in a database of pediatric hearing-impaired patients. SETTING: A tertiary care pediatric referral center. PATIENTS: Seventy-one children with EVA and screening results for SLC26A4 mutations. MAIN OUTCOME MEASURES: Genetic screening results, audiometric thresholds, and radiographic temporal bone measurements. RESULTS: Seventy-one children with EVA were screened for SLC26A4 mutations. Mutations were found in 27% of children overall, while only 8% had biallelic mutations. The mean initial pure-tone average (PTA) was 59 dB; the mean final PTA was 67 dB. A bilateral EVA was found in 48 (67%) of the children; a unilateral EVA was found in 23 (33%). Progressive hearing loss (in at least 1 ear) was seen in 29 (41%) of the patients. The strongest genotype-phenotype interaction was seen in children with a bilateral EVA. Among children with SLC26A4 mutations, there was a significantly wider vestibular aqueduct at the midpoint and a wider vestibule width (P < .05) than in children without the mutation. Among patients with a bilateral EVA, children with any SLC26A4 mutation were more likely to have a more severe final PTA (64 dB vs 32 dB), larger midpoint measurement (2.1 vs 1.1 mm), and larger operculum measurement (3.0 vs 2.0 mm) than those without the mutation in their better-hearing ear (P < .05). CONCLUSIONS: In a population of pediatric patients with an EVA and hearing loss, SLC26A4 mutations are a contributor to the phenotype. Our data suggest that other genetic factors also have important contributions to this phenotype. The presence of an abnormal SLC26A4 allele, even in the heterozygous state, was associated with greater enlargement of the vestibular aqueduct, abnormal development of the vestibule, and possibly a stable hearing outcome.     

Grade and laterality of intraventricular haemorrhage to predict 18-22 month neurodevelopmental outcomes in extremely low birthweight infants

Aim: To determine whether extremely low‐birthweight (ELBW) infants with bilateral compared to unilateral intraventricular haemorrhage (IVH) have worse neurodevelopmental outcomes at 18–22 months. Methods: A total of 166 ELBW infants (<1000 g) admitted to a Cincinnati NICU from 1998 to 2005 with a head ultrasound showing Grade I–IV IVH and neurodevelopmental assessment at 18–22 months corrected age were included. Multivariable linear and logistic regression models were developed to determine the impact of laterality and grade of IVH and other clinical variables to predict scores on the Bayley Scales of Infant Development, Second Edition, Mental Development Index and Psychomotor Development Index and the combined outcome of neurodevelopmental impairment (NDI). Results: Infants with bilateral grade IV IVH had lower adjusted mean Bayley scores compared with infants with unilateral grade IV IVH. For grades I, II and III IVH, bilaterality of IVH was not associated with lower mean Bayley scores. Infants with grade IV IVH had the highest odds of NDI. The probability of NDI increased with sepsis and postnatal steroid use. Conclusion: ELBW infants with bilateral compared to those with unilateral grade IV IVH had worse neurodevelopmental outcomes. Infants with grades I–III IVH had similar outcomes whether they had unilateral or bilateral IVH.     

Risk of infant anemia is associated with exclusive breast-feeding and maternal anemia in a Mexican cohort

The WHO recommends exclusive breast-feeding (EBF) for the first 6 mo of life to decrease the burden of infectious disease. However, some are concerned about the effect of EBF >6 mo on iron status of children in developing countries in which anemia is prevalent. This study examines the risk of anemia in relation to the duration of EBF and maternal anemia in a birth cohort studied between March 1998 and April 2003. All infant birth weights were >or=2.2 kg. All mothers received home-based peer counseling to promote EBF. Infant feeding data were collected weekly. Nurses measured hemoglobin (Hb) values every 3 mo. Hb was measured in 183 infants at 9 mo of age. Anemia at 9 mo was defined as a Hb value <100 g/L. EBF was defined by WHO criteria and ranged in duration from 0 to 31 wk. At 9 mo, Hb (mean +/- SEM) was 114 +/- 0.9 g/L; 23 children (12.5%) had Hb levels <100 g/L. EBF >6 mo, but not EBF 4-6 mo, was associated with increased risk of infant anemia compared with EBF <4 mo (odds ratio=18.4, 95% CI=1.9, 174.0). Maternal anemia was independently (P=0.03) associated with a 3-fold increased risk of infant anemia. These associations were not explained by confounding with other maternal or infant factors. By linear regression, a lower infant Hb at 9 mo was associated with increased EBF duration among mothers who had a history of anemia (beta=-0.07, P=0.003), but not among mothers with no history of anemia. Infants who are exclusively breast-fed for >6 mo in developing countries may be at increased risk of anemia, especially among mothers with a poor iron status; greater attention to this issue is warranted.