Kaukab Rajput

Cochlear implantation in individuals with Usher type 1 syndrome

OBJECTIVE To analyze the occurrence of the Usher type 1 (USH1) gene mutations in cochlear implant recipients with deaf-blind Usher syndrome, and to assess the potential effect of these genes and other factors on the therapeutic outcome. STUDY DESIGN Case series study of nine patients with the phenotypic diagnosis of USH1. METHODS AND SUBJECTS Mutation analysis of four USH1 genes (MYO7A, USH1C, CDH23, and PCDH15) by single strand conformational polymorphism (SSCP) and direct sequencing methods. Pre- and post-implantation audiologic tests including pure tone audiometry, speech perception measures, and qualitative assessment of auditory performance. Nine USH1 patients who received their cochlear implants at the University of Miami Ear Institute, Miami, FL, USA, and at the Department of Cochlear Implants, Great Ormond Street Hospital for Children, London, UK. RESULTS DNA samples from five of the nine patients were available for mutation analysis. Three of the five patients were found to carry USH1 mutations including two with a truncated mutation in CDH23 and one being a digenic inheritance with mutations in CDH23 and PCDH15. We may have failed to detect mutations in the amplicons analyzed, as neither SSCP nor direct sequencing, even combined, detects all mutations present. Our failure to detect mutations in all five patients may also confirm the genetic heterogeneity of USH1 and additional USH1 loci remain to be mapped. Pre-implantation assessment indicated that all of the subjects were pre-linguistically profoundly deaf, had no consistent response to sound, had varying degrees of auditory-oral habilitation. Age at implantation ranged from 2 to 11 years. There was post-implantation improvement in sound detection and speech recognition measures in closed-set format in all patients. Children implanted at an age of 3 years or less showed good open-set speech perception with lip-reading. All patients are implant users. Those patients who do not show open-set perception still use the cochlear implant as an adjunct of lip-reading or total communication. CONCLUSION Testing for mutations in the USH1 genes allows early identification and intervention of children with USH1; timely intervention is important to maximize the development of useful auditory-oral communication skills prior to the onset of the visual impairment.

Recurrent mutations in the deafness gene GJB2 (connexin 26) in British Asian families

Editor—Mutations in GJB2 , the connexin 26 (Cx26) gene, are thought to account for over 50% of autosomal recessive, non-syndromic, congenital deafness, the most common form of genetic deafness1 2 and 10-30% of sporadic cases.2 3 Over 50 recessive mutations in the GJB2 gene have been reported since it was originally described4 (the connexin 26 (GJB2) deafness homepage athttp://www.iro.es/cx26deaf.html). The most common mutation is a deletion of a guanosine nucleotide at position 30-35 (35delG), accounting for approximately 30-63% of mutations in white populations with a carrier frequency of 1:31 in Mediterranean populations.1 2 However, the 35delG mutation is present at a lower prevalence in different ethnic groups,5-8 with other mutations occurring at a higher prevalence, such as 167delT in the Jewish population.9-12 Both the high carrier frequency of GJB2 mutations and the prevalence of non-35delG mutations in non-white populations implies that mutations other than 35delG may be more common in non-white ethnic minorities who have settled in the UK, particularly those in which consanguinity is prevalent. In order to examine strategies suitable for sensitive, medium throughput mutation detection in GJB2 , we used denaturing high performance liquid chromatography (DHPLC) to screen for mutations in a cohort of 51 multi-ethnic patients with non-syndromic deafness who presented at our centre for genetic counselling. We found that DHPLC detected all the control mutations in the sample and that no mutations were identified by sequencing that were not detected by DHPLC. Three mutations, W24X, W77X, and Q124X, found in Indian, Pakistani, and Bangladeshi families in this study, have been previously observed in families from the Indian subcontinent, suggesting that they may be common mutations in these ethnic groups. Fifty one subjects with non-syndromic hearing loss were ascertained through genetic counselling and audiological medicine clinics at Great …

Event-related potentials in pediatric cochlear implant patients.

Objective: The main objective of this study was to assess the correlation of auditory event related potential (ERP) measures with behavioral assessment data to identify if ERPs including mismatch negativity (MMN) can be used to categorize cochlear implant patients into good and poor performers. Design: We investigated auditory event–related potentials to standard and deviant speech stimuli presented in a pseudorandom sequence in 35 cochlear implant patients between the ages of 7 and 17 yr. We compared the occurrence, latencies, and amplitudes of P1, N2, and MMN with overall behavioral outcome in these children. Behavioral measures included category of auditory performance scores and speech intelligibility rating scores. Results: Auditory ERPs in response to standard stimuli were identifiable in 30 of 35 patients, demonstrating a major positive component (P1) followed by a negativity (N2) with absence of N1 in all patients. The P1 component in prelingually deaf patients showed a statistically significant reduction in its latency with increasing duration of implant use. MMN was recorded in 80–85% of star performers but in only 15–20% of poor performers. Patients with higher SIR scores demonstrated statistically significant longer duration of MMN compared with those with a lower SIR score. Conclusions: These results indicate that MMN can be used to assess the functional status of the auditory cortex in terms of auditory memory and discrimination in young children with cochlear implants and may provide an objective mechanism for differentiating good from poor performers.

The bony cochlear nerve canal in children with absent or hypoplastic cochlear nerves

OBJECTIVE To correlate presence and size of the bony cochlear nerve canal [BCNC] with size of the internal auditory meatus [IAM] on CT in children with absent or hypoplastic cochlear nerves [CNs] as compared to age matched controls. METHODS This retrospective case-notes review was based in the departments of Cochlear Implantation and Neuroradiology at a tertiary paediatric hospital. Twenty-five ears of fifteen children (subjects) with profound sensorineural deafness (SND) and absent or hypoplastic CN on MRI scan were compared to age matched controls. Two groups of controls were included; a control group of nineteen ears of twelve children with normal hearing or conductive hearing loss [control group 1] and a second control group of twenty one ears of eleven children with severe to profound hearing loss related to GJB2 mutations [control group 2]. Both control groups had evidence of the presence of the CN. Two neuroradiologists independently assessed presence and size of BCNC and IAM on CT and presence of CN on MRI in subjects and controls. The BCNC and IAM size was compared between subjects and both control groups. The presence of BCNC was correlated with the IAM size on CT, presence/absence of CN on MRI and audiological evaluation in subjects. RESULTS The mean IAM width was significantly smaller in subjects as compared to controls. The BCNC was absent in 17/25 subject ears and present in all control ears. Absent BCNC correlated with a narrow IAM in 13/17 subject ears. Presence of the BCNC supported presence of a CN although this was not seen on MRI. However, BCNC absence may be associated with presence of a CN as was seen in two subject ears. Five subject ears out of 22 [22%] with absent CN on MRI had other evidence of a present cochlear nerve. CONCLUSIONS BCNC is an additional parameter to assess presence of the cochlear branch of the CN. Presence of the BCNC may indicate cochlear nerve presence. Caution should be used in assessing candidacy of cochlear implants based on MRI alone and a combination of imaging and audiological tests should be used to assess presence of the CN.

Orthographic influences, vocabulary development, and phonological awareness in deaf children who use cochlear implants

In the current study, we explore the influence of orthographic knowledge on phonological awareness in children with cochlear implants and compare developmental associations to those found for hearing children matched for word reading level or chronological age. We show an influence of orthographic knowledge on syllable and phoneme awareness in deaf and hearing children, but no orthographic effect on rhyme awareness. Nonorthographic rhyme awareness was a significant predictor of reading outcomes for all groups. However, whereas receptive vocabulary knowledge was the most important predictor of word reading variance in the cochlear implant group, rhyme awareness was the only important predictor of word reading variance in the reading level matched hearing group. Both vocabulary and rhyme awareness were equally important in predicting reading in the chronological age-matched hearing group. The data suggest that both deaf and hearing children are influenced by orthography when making phonological judgments, and that phonological awareness and vocabulary are both important for reading development.

Efficacy and safety of canakinumab therapy in paediatric patients with cryopyrin-associated periodic syndrome: a single-centre, real-world experience

OBJECTIVE The aim of this study was to determine the short- and long-term efficacy and safety of 8-weekly canakinumab therapy in children with cryopyrin-associated periodic syndromes (CAPS) in routine clinical practice. METHODS A single-centre observational study was performed. Patients were assessed every 8 weeks at a dedicated clinic. Standardized assessments were the 10-domains DAS for CAPS, acute phase reactants (APRs), physicians global assessment of disease activity, Child Health Assessment Questionnaire (CHAQ) and Child Health Questionnaire Parent Form 28 (CHQPF-28). The primary endpoint was clinical improvement, defined as a reduction of DAS score 8 weeks after commencing therapy. Secondary endpoints included sustained clinical improvement in APRs, relapses, CHAQ score and CHQPF-28 score. RESULTS Ten children with CAPS [eight Muckle-Wells syndrome (MWS), two chronic infantile cutaneous neurological articular (CINCA); median age 6.3 years] received 8-weekly canakinumab treatments at 2-8.7 mg/kg for a median of 21 months (range 12-31 months). Nine of 10 patients improved after the first dose: baseline median DAS of 7.5/20 decreased to 3.5/20 at 8 weeks (P = 0.04). This clinical improvement was sustained at a median follow-up of 21 months (range 12-31 months). Children with CINCA required higher doses of canakinumab than those with MWS. CHAQ and CHQ scores indicated improvement in functioning and health-related quality of life (HRQoL). Treatment was well tolerated, with no injection site reactions and no serious infections. CONCLUSION Canakinumab, although costly, is a safe and effective treatment for CAPS in children, leading to sustained improvement in disease activity, serological markers, functional ability and HRQoL.

Homozygosity for piebaldism with a proven KIT mutation resulting in depigmentation of the skin and hair, deafness, developmental delay and autism spectrum disorder.

North West Thames Regional Genetics Service (Kennedy Galton Centre), Northwick Park Hospital, NWLH NHS Trust, Harrow, Departments of Paediatrics, Community Paediatrics, Hillingdon Hospital, Uxbridge, Middlesex, Departments of Ophthalmology, Audiological Medicine, Great Ormond Street Hospital, London, UK and Molecular Genetics Laboratory, University of Munich, Munich, Germany Correspondence to Angela F. Brady, FRCP, PhD, North West Thames Regional Genetics Service (Kennedy Galton Centre), Northwick Park Hospital, NWLH NHS Trust, Harrow HA1 3UJ, UK Tel: + 44 20 8869 2795; fax: + 44 20 8869 3106; e-mail: a.brady@imperial.ac.uk

Vestibular function in children with auditory neuropathy spectrum disorder.

OBJECTIVE Children with auditory neuropathy spectrum disorder (ANSD) account for about 10% of paediatric patients referred for cochlear implantation. Vestibulopathy may be associated with ANSD, and may have implications when formulating management plans in this patient group. We wanted to determine the incidence and predictive factors for vestibulopathy in this patient group to guide vestibular testing in this patient population, and give insight to the aetiology of ANSD. METHODS We reviewed the outcomes of vestibular function testing in a cohort of paediatric patients with ANSD. RESULTS Probable or definite vestibulopathy was seen in 42% of patients who were tested. Vestibulopathy was associated with medical co-morbidities, but was not associated with imaging findings. CONCLUSIONS Vestibulopathy is relatively prevalent in this patient group, and should be considered when planning the investigation and management of children with ANSD.

Outcomes of meningococcal serogroup B disease: findings from a nationally representative case-control study

Aims There remain over 1000 cases of meningococcal serogroup B (MenB) disease in the UK each year. Vaccines to prevent other causes of meningitis and septicaemia have been successfully introduced into many countries. Estimates of the sequelae of MenB disease in the modern era are needed to inform the development and introduction of future vaccines. Methods The authors present interim results from a nationally representative case-control study from five English regions. Cases were identified via the Meningococcal Reference Laboratory and controls via case general practitioners. Consenting subjects underwent a 2.5-h standardised assessment of hearing (audiometry), IQ and other cognitive function, psychological function and quality of life. Analyses were undertaken adjusted for age and sex. The study received ethics approval and was funded by the Meningitis Trust. Results Data were available for 153 cases and 100 controls. Compared with controls, MenB survivors had lower verbal IQ (case mean 99, control mean 104; p=0.02), performance IQ (98 vs 102; p=0.04), were more likely to have any mental health disorder (24% vs 11%; p=0.04) and had poorer memory (p=0.008). Three survivors (2%) had cochlear implants compared with no controls. However, there were no significant differences between survivors and controls in proportions with mild or moderate hearing loss. Survivors were also more likely to receive Disability Living Allowance (9% vs 1%; p=0.009) and additional educational support (19% vs 6%; p=0.01). Conclusions These interim results suggest MenB disease is associated with a significant burden of sequelae in survivors. These data will form the basis for cost-effectiveness analyses of new MenB vaccines.

Expert opinion: Assessing cochlear implant candidacy and progress for people with English as an additional language

Special considerations relating to cochlear implants (CIs) are necessary for deaf people for whom English is an additional language (EAL). The audiological and pre-linguistic skills criteria for CI candidacy are the same for children with EAL as for children from English-speaking families. However, thorough assessment is not straightforward, for example, requiring employment of experienced interpreters. To ensure family engagement and thus appropriate support in the home, clear understanding of the familys social and cultural framework and of their needs and requirements is essential. Equally, the family must be enabled to understand the implications of CI. Additional training of staff in CI teams may be needed. This article will address these and other issues for children and also consider the situation for adults.