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1.
J Paediatr Child Health ; 58(2): 288-294, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34520069

ABSTRACT

AIM: This study aimed to determine the feasibility and parental acceptability of screening for congenital cytomegalovirus (cCMV) through saliva polymerase chain reaction in infants who did not pass their newborn hearing screening. Additionally, the utility (i.e. time to diagnosis and treatment) of this enhanced clinical pathway was evaluated. METHODS: The study was conducted through the Victorian Infant Hearing Screening Programme (VIHSP) across four maternity hospitals in Melbourne, Australia, during June 2019-March 2020. Parents were approached by VIHSP staff about obtaining a test for cytomegalovirus (CMV) at the time of their baby's second positive ('refer') result on the VIHSP screen. Participating parents collected a saliva swab for CMV polymerase chain reaction from their infants. Feasibility was determined by the proportion of 'referred' infants whose parents completed the salivary CMV screening test ≤21 days of life. Acceptability was measured through parent survey. RESULTS: Of 126 eligible families, 96 (76.0%) had salivary screening swabs taken ≤21 days of life. Most families (>92.0%) indicated that screening was acceptable, straightforward and thought testing their baby for cCMV was a good idea. One infant screened positive on day 30, was diagnosed with cCMV via confirmatory testing by day 31 and commenced valganciclovir on day 32. CONCLUSIONS: Obtaining a saliva sample to screen for cCMV in infants who do not pass their newborn hearing screen is feasible and appears acceptable to parents. This targeted cCMV screening method could be an option where mothers are rapidly discharged from hospital, especially in the context of the COVID-19 pandemic.


Subject(s)
COVID-19 , Cytomegalovirus , Feasibility Studies , Female , Hearing , Humans , Infant , Infant, Newborn , Neonatal Screening , Pandemics , Pregnancy , SARS-CoV-2
3.
Neurology ; 94(20): e2148-e2167, 2020 05 19.
Article in English | MEDLINE | ID: mdl-32345733

ABSTRACT

OBJECTIVE: Determining the genetic basis of speech disorders provides insight into the neurobiology of human communication. Despite intensive investigation over the past 2 decades, the etiology of most speech disorders in children remains unexplained. To test the hypothesis that speech disorders have a genetic etiology, we performed genetic analysis of children with severe speech disorder, specifically childhood apraxia of speech (CAS). METHODS: Precise phenotyping together with research genome or exome analysis were performed on children referred with a primary diagnosis of CAS. Gene coexpression and gene set enrichment analyses were conducted on high-confidence gene candidates. RESULTS: Thirty-four probands ascertained for CAS were studied. In 11/34 (32%) probands, we identified highly plausible pathogenic single nucleotide (n = 10; CDK13, EBF3, GNAO1, GNB1, DDX3X, MEIS2, POGZ, SETBP1, UPF2, ZNF142) or copy number (n = 1; 5q14.3q21.1 locus) variants in novel genes or loci for CAS. Testing of parental DNA was available for 9 probands and confirmed that the variants had arisen de novo. Eight genes encode proteins critical for regulation of gene transcription, and analyses of transcriptomic data found CAS-implicated genes were highly coexpressed in the developing human brain. CONCLUSION: We identify the likely genetic etiology in 11 patients with CAS and implicate 9 genes for the first time. We find that CAS is often a sporadic monogenic disorder, and highly genetically heterogeneous. Highly penetrant variants implicate shared pathways in broad transcriptional regulation, highlighting the key role of transcriptional regulation in normal speech development. CAS is a distinctive, socially debilitating clinical disorder, and understanding its molecular basis is the first step towards identifying precision medicine approaches.


Subject(s)
Apraxias/genetics , Speech Disorders/genetics , Speech/physiology , Transcription Factors/genetics , Adolescent , Apraxias/diagnosis , Apraxias/physiopathology , Child , Child, Preschool , Female , GTP-Binding Protein alpha Subunits, Gi-Go/genetics , Genetic Association Studies , Humans , Male , Speech Disorders/diagnosis , Speech Disorders/physiopathology
4.
Eur J Hum Genet ; 28(5): 587-596, 2020 05.
Article in English | MEDLINE | ID: mdl-31827275

ABSTRACT

Congenital hearing impairment (HI) is the most common sensory impairment and can be isolated or part of a syndrome. Diagnosis through newborn hearing screening and management through early intervention, hearing aids and cochlear implantation is well established in the Australian setting; however understanding the genetic basis of congenital HI has been missing. This population-derived cohort comprised infants with moderate-profound bilateral HI born in the 2016-2017 calendar years, detected through newborn hearing screening. Participants were recruited through an integrated paediatric, otolaryngology and genetics HI clinic and offered whole exome sequencing (WES) on a HiSeq4000 or NextSeq500 (Illumina) platform with a targeted average sequencing depth of 100x and chromosome microarray on the Illumina Infinium core exome-24v1.2 platform. Of those approached, 68% (106/156) consented to participate. The rate of genetic diagnosis was 56% (59/106), significantly higher than standard of care (GJB2/6 sequencing only), 21% (22/106). There were clinical implications for the 106 participants: 36% required no further screening, 9% had tailored screening initiated, 2% were offered treatment and 4% had informed care for a complex neurodevelopmental syndrome. WES in this cohort demonstrates the range of diagnoses associated with congenital HI and confirms the genetic heterogeneity of congenital HI. The high diagnostic yield and clinical implications emphasises the need for genomic sequencing to become standard of care.


Subject(s)
Exome Sequencing/standards , Genetic Testing/standards , Hearing Loss/genetics , Neonatal Screening/standards , Female , Genetic Testing/methods , Hearing Loss/diagnosis , Humans , Infant , Infant, Newborn , Male , Neonatal Screening/methods , Sensitivity and Specificity , Exome Sequencing/methods
6.
J Autism Dev Disord ; 47(7): 2010-2022, 2017 07.
Article in English | MEDLINE | ID: mdl-28389756

ABSTRACT

High levels of stress and anxiety are common in children with Autism Spectrum Disorder (ASD). Within this study of school-aged children (20 male, 6 female) we hypothesised that functional hearing deficits (also pervasive in ASD) could be ameliorated by auditory interventions and that, as a consequence, stress levels would be reduced. The use of Ear-Level Remote Microphone devices and Classroom Amplification systems resulted in significantly improved listening, communication and social interaction and a reduction in physiologic stress levels (salivary cortisol) in both one-on-one and group listening situations.


Subject(s)
Autism Spectrum Disorder/psychology , Heart-Assist Devices , Stress, Psychological/prevention & control , Autism Spectrum Disorder/complications , Child , Female , Humans , Male , Speech Perception
7.
BMJ Paediatr Open ; 1(1): e000119, 2017.
Article in English | MEDLINE | ID: mdl-29637142

ABSTRACT

INTRODUCTION: The aetiology of congenital hearing loss is heterogeneous, and in many infants a genetic cause is suspected. Parents face a diagnostic odyssey when searching for a cause of their infant's hearing loss. Through the Melbourne Genomics Health Alliance, a prospective cohort of infants will be offered whole-exome sequencing (WES) with targeted analysis in conjunction with chromosome microarray to determine the genetic causes of congenital hearing loss. Parents will also be offered the opportunity to receive additional results from their infant's WES. METHODS: Eligible infants will be identified through the Victorian Infant Hearing Screening Program and offered an appointment in a paediatrician-run clinic, a genetics assessment and enrolment in the Victorian Childhood Hearing Impairment Longitudinal Databank. If parents consent to WES, genes causing deafness will be analysed and they can choose to obtain additional findings. For the additional results component, a modified laboratory protocol has been designed for reporting of results in the absence of a relevant phenotype. Parents' experience of being offered WES will be evaluated using surveys. DISCUSSION: This project will provide descriptive analysis of the genetic aetiology of congenital hearing loss in this cohort and may provide data on genotype-phenotype correlations. Additionally, choices regarding additional findings will be analysed. Participants will represent a diverse cross section of the population, increasing the ability to generalise results beyond the study group. Evaluation surveys will allow analysis of preferences around counselling, usefulness of a decision aid and adequacy of information provision.

8.
J Pediatr ; 164(2): 352-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24183205

ABSTRACT

OBJECTIVES: To evaluate both monaural and binaural processing skills in a group of children with autism spectrum disorder (ASD) and to determine the degree to which personal frequency modulation (radio transmission) (FM) listening systems could ameliorate their listening difficulties. STUDY DESIGN: Auditory temporal processing (amplitude modulation detection), spatial listening (integration of binaural difference cues), and functional hearing (speech perception in background noise) were evaluated in 20 children with ASD. Ten of these subsequently underwent a 6-week device trial in which they wore the FM system for up to 7 hours per day. RESULTS: Auditory temporal processing and spatial listening ability were poorer in subjects with ASD than in matched controls (temporal: P = .014 [95% CI -6.4 to -0.8 dB], spatial: P = .003 [1.0 to 4.4 dB]), and performance on both of these basic processing measures was correlated with speech perception ability (temporal: r = -0.44, P = .022; spatial: r = -0.50, P = .015). The provision of FM listening systems resulted in improved discrimination of speech in noise (P < .001 [11.6% to 21.7%]). Furthermore, both participant and teacher questionnaire data revealed device-related benefits across a range of evaluation categories including Effect of Background Noise (P = .036 [-60.7% to -2.8%]) and Ease of Communication (P = .019 [-40.1% to -5.0%]). Eight of the 10 participants who undertook the 6-week device trial remained consistent FM users at study completion. CONCLUSIONS: Sustained use of FM listening devices can enhance speech perception in noise, aid social interaction, and improve educational outcomes in children with ASD.


Subject(s)
Autistic Disorder/rehabilitation , Cues , Hearing Aids/statistics & numerical data , Hearing Disorders/therapy , Hearing , Speech Perception/physiology , Adolescent , Audiometry , Autistic Disorder/complications , Autistic Disorder/physiopathology , Child , Female , Follow-Up Studies , Hearing Disorders/etiology , Hearing Disorders/physiopathology , Hearing Tests , Humans , Male , Treatment Outcome
9.
Autism ; 16(6): 627-40, 2012 Nov.
Article in English | MEDLINE | ID: mdl-21949004

ABSTRACT

The relationship of motor proficiency with emotional/behavioural disturbance, autistic symptoms and communication disturbance was investigated in children diagnosed with autism and Asperger's disorder (AD). The Movement Assessment Battery for Children was used as a measure of motor impairment, and the Developmental Behavioural Checklist was used as a measure of emotional/behavioural disturbance in the following groups: AD (n = 22), high functioning autism (HFA) (n = 23), LFA (n = 8) and typically developing children (n = 20). The HFA group had more difficulty with motor items, such as ball skills and balance, than did the AD group. There were significant positive correlations between impairments in motor proficiency (in particular ball skills and balance) and emotional/behavioural disturbance, autistic symptoms and communication disturbance. These findings are consistent with the hypothesis that there are qualitative and quantitative differences in the motor profile between autism and AD. In addition, the association between motor proficiency impairment and emotional/behavioural disturbance in autism and AD emphasizes the importance for screening of co-occurring emotional/behavioural symptoms in individuals with motor difficulties. These findings have implications for the potential use of adjunct motor measures in the diagnosis and definition of autism spectrum disorders.


Subject(s)
Affective Symptoms/physiopathology , Asperger Syndrome/physiopathology , Autistic Disorder/physiopathology , Child Behavior Disorders/physiopathology , Movement Disorders/physiopathology , Adolescent , Affective Symptoms/etiology , Asperger Syndrome/complications , Autistic Disorder/complications , Case-Control Studies , Child , Child Behavior Disorders/etiology , Communication Disorders/etiology , Communication Disorders/physiopathology , Female , Humans , Male , Motor Skills , Movement Disorders/etiology
10.
Pediatrics ; 118(5): 1842-51, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17079553

ABSTRACT

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.


Subject(s)
Hearing Loss, Sensorineural/epidemiology , Child , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Severity of Illness Index
12.
J Paediatr Child Health ; 41(4): 197-200, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15813874

ABSTRACT

OBJECTIVE: Universal Newborn Hearing Screening (UNHS) programmes have been widely implemented, but their costs, benefits and long-term logistics remain to be clearly defined. There are few rigorous evaluations of alternative strategies. In this paper, we evaluate the performance of the distraction test component of the two-tiered Victorian Infant Hearing Screening Program (VIHSP). METHODS: All babies born in the State of Victoria, Australia in 1993 who survived the neonatal period were screened for the presence of risk factors for hearing loss. Those at-risk were referred for Auditory Brainstem Evoked Response (ABR) screening by a professional audiologist. All others were screened by modified distraction test at age 7-9 months. This birth cohort was followed through age 6 for diagnoses of congenital hearing loss resulting in fitting of hearing aids. Estimates of false-positives, false-negatives, sensitivity, specificity and positive predictive values were determined for the distraction test as a population screen. Ages at diagnosis and aid fitting for screen failures with hearing loss were compared with current goals. RESULTS: For targeted (moderate or greater-aided) losses, the distraction test yielded eight (0.02%) documented false-negatives (one severe and seven moderate) and an estimated 4265 (99%) false-positives. Distraction test sensitivity was 65%, specificity 91% and PPV 0.3%. Mean age at diagnosis for distraction test failures across all severities, including mild losses, was 23 (SD 18) months with a mean age at aid fitting of 26 (SD 20) months. CONCLUSIONS: The distraction test screen generated large numbers of false-positives and a significant number of false-negatives, performing particularly poorly with moderate losses. Ages at diagnosis and aid fitting for screen failures were far older than currently accepted goals. There is little evidence that the distraction test can be made to work acceptably as a population-based screen.


Subject(s)
Evoked Potentials, Auditory , Hearing Loss/classification , Hearing Tests/methods , Child , Child, Preschool , Cohort Studies , Hearing Loss/congenital , Humans , Infant , Predictive Value of Tests , Severity of Illness Index , Victoria
13.
Int J Audiol ; 42(7): 385-90, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14582634

ABSTRACT

The aim of this study was to report the incidence, prevalence and clinical characteristics of congenital hearing loss sufficient to require hearing aid fitting in the first 6 years of life for the 1993 birth cohort of the state of Victoria (population 4.4 million), Australia. In 1993, 64,116 infants born in the state of Victoria survived the neonatal period. Subjects included all children with congenital hearing loss for which hearing aids were fitted, at any time up to and including 31 December 1999, when the youngest member of the cohort reached 6 years of age. Data on the degree, type and etiology of hearing loss were available from the Australian Hearing database for all subjects. Sociodemographic and health data were available from the Victorian Infant Hearing Screening Program (VIHSP) and parent questionnaires. The known prevalence of identified congenital hearing loss increased as the cohort aged. By the time the youngest member had reached the age of 6 years, 134 children (78 boys, 56 girls) had been fitted with hearing aids for permanent congenital hearing loss of any degree (2.09/1000). Fifty-four (40%) of these had known mild losses (20-40 dB HL). The prevalence of known moderate or greater loss (> 40 dB HL) was 1.12/1000; the data suggest that over 90% could have been detectable by neonatal hearing screening. A further seven children from the birth cohort were fitted with hearing aids due to acquired forms of hearing loss (0.11/1000). The etiology was known in only 57 (43%) congenital cases, with known non-syndromal genetic causes accounting for 21 (37%) of these. This study reports on the prevalence of congenital hearing loss requiring hearing aid fitting for an entire birth cohort. These data indicate the possible yield from neonatal screening, and hence the likely benefit of such screening. For a large proportion of cases, the etiology remains unknown. These data have implications for health service delivery and illustrate the usefulness of a population database in monitoring the prevalence of congenital hearing loss.


Subject(s)
Hearing Loss/congenital , Hearing Loss/epidemiology , Child , Child, Preschool , Cohort Studies , Female , Genetic Counseling , Hearing Aids , Hearing Loss/rehabilitation , Humans , Incidence , Infant , Male , Prevalence , Socioeconomic Factors , Victoria/epidemiology
14.
Fertil Steril ; 79(3): 512-6, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12620432

ABSTRACT

OBJECTIVE: To investigate the possibility that children born after ICSI were at increased risk for neurodevelopmental delay. DESIGN: Retrospective case-control study. SETTING: IVF clinic. PATIENT(S): Fifty-eight singleton children born after ICSI and 38 normally conceived singleton children (controls), matched for relevant sociodemographic characteristics, from Australia and 208 case-patients and 221 controls from the United Kingdom. MAIN OUTCOME MEASURE(S): Antenatal and perinatal, and sociodemographic characteristics; physical health, including congenital abnormalities; and neurodevelopment by using the Griffiths scales of mental development. RESULT(S): Eighty-five percent of case-patients and 96% controls were assessed at a mean age of 13 months. Neurodevelopmental scores were similar in all children. Perinatal outcome was similar, apart from more caesarean sections in the case-patients. Rates of congenital anomalies were similar (5.6% among case-patients vs. 5.7% among controls). Children from fathers with oligozoospermia showed no extra problems. Children born after ICSI in the United Kingdom and Australia were similar. CONCLUSION(S): Children conceived after ICSI did not differ from their naturally conceived peers in physical health or development at ages up to 15 months.


Subject(s)
Developmental Disabilities/epidemiology , Sperm Injections, Intracytoplasmic , Adult , Alcohol Drinking/epidemiology , Australia/epidemiology , Case-Control Studies , Cohort Studies , Humans , Infant , Maternal Age , Retrospective Studies , United Kingdom/epidemiology
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