Audiology and Speech Pathology - Theses
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ItemSpeech and language in chromatin-related disorders( 2023-03)Background. Diagnosis of a speech or language disorder can impose lifelong impacts on literacy, social skills, and employment outcomes. Rare genetic neurodevelopmental disorders are often accompanied by speech and language disorders with subsequent deleterious impacts. Although genetic neurodevelopmental disorders are individually rare, collectively they are common and contribute to a vast number of individuals living with speech and language disorders across the world. Chromatin-related disorders are one class of genetic disorder, each caused by a perturbed gene important for chromatin function. Aims. My thesis has three aims, which in turn, form three studies: (1) To provide a systematic review of speech and language outcomes across chromatin-related neurodevelopmental disorders, (2) To provide detailed speech and language phenotyping in individuals with pathogenic variants in KAT6A, namely KAT6A syndrome (also known as Arboleda-Tham syndrome), and to report genotype-phenotype correlation. (3) To provide a comprehensive phenotype of the speech and language profile of individuals with Koolen-de Vries syndrome (caused by KANSL1 variants or 17q21.31 deletions). Methods. Methods for each sub-study are detailed below: (1) A literature search was conducted on 70 chromatin-related genes (collated from two key chromatin disorder-related publications), to identify speech and language findings in human-based studies, (2) Participants aged 6 months to adulthood, with a confirmed genetic diagnosis of KAT6A syndrome (caused by a pathogenic KAT6A variant) were recruited through clinical collaborators, the Australian Association of Clinical Geneticists, and international family support groups. Exclusion criteria were the presence of any other confirmed genetic variant or syndrome likely to impact the clinical phenotype. Speech, language, non-verbal communication, feeding, and adaptive behaviour were assessed using a battery of standardised and formal assessments, and data were analysed in the context of the wider medical and neurodevelopmental profile. (3) Participants aged 6 months to adulthood, with a confirmed diagnosis of Koolen-de Vries syndrome (caused by either a pathogenic KANSL1 variant or 17q21.31 deletion) were recruited through a research database held at the authors’ institution, clinical collaborators, and an international family support group. Exclusion criteria were the presence of any other confirmed genetic variant or syndrome likely to impact the clinical phenotype. Speech (including an in-depth fluency questionnaire), language, feeding, and adaptive behaviour were assessed using a battery of standardised and formal assessments, which were analysed in the context of the wider medical and neurodevelopmental profile. Results. Results for each sub-study are described below: (1) 3932 studies were identified and screened and 112 were systematically reviewed. Of the 112 publications, 35 reported on standardised or formal speech and language outcomes measures, while only five systematically delineated speech and language phenotypes. Data regarding speech and language outcomes were available for 40 genes. Communication impairment was a core phenotypic feature noted across all chromatin disorders, presenting as severe in ten, moderate in five, mild in seven, and mixed in seven. 11 had limited data to determine severity. Motor speech phenotypes and regression were more common in disorders relating to epigenetic writers and readers. (2) Forty-nine individuals (25 females; aged 1;5–31;10) were included with KAT6A syndrome. Co-occurring medical and neurodevelopmental phenotypes included moderate to severe intellectual disability or developmental delay (42/45), vision and eye anomalies (37/48), gastrointestinal concerns (33/48), and sleep disturbance (31/48). Most (36/49) were minimally-verbal. Verbal participants (13/49) displayed complex and co-occurring speech diagnoses including phonological impairments and childhood apraxia of speech (CAS). Adaptive behaviour including communication (receptive/expressive language), socialisation, motor skills and daily living skills were all severely impaired. Late truncating variants were associated with poorer communication, daily living skills, and socialization outcomes. (3) Eighty-one individuals with KdVS were evaluated (35 female, mean age 9y 10mo), 56 harbouring typical 17q21.31 deletions. Concurrent medical and neurodevelopmental features included intellectual disability (49/56), eye and vision disturbances (48/81), structural brain anomalies (33/62), sleep disturbance (33/81), and musculoskeletal abnormalities (32/81). Most individuals were verbal (62/81), and the remainder were successful in using alternative and augmentative communication (AAC) to communicate. Verbal participants had diagnoses of CAS (39/61), dysarthria (28/61), and stuttering (36/47). Stuttering followed a unique trajectory of later onset and fluctuating presence, compared to the broader population of individuals with stuttering in the absence of KdVS. Receptive and expressive language abilities were commensurate, rather than one domain being stronger or weaker than the other. Literacy skills were a relative weakness. Social competence, behaviour, and coping skills represented relative strengths. Discussion. Individual chromatin-regulating genes cause distinct profiles of communication, and these have important implications for identification, prognosis, and clinical recommendations for such disorders. The detailed phenotyping I have provided for KAT6A syndrome and KdVS is invaluable for determining prognostic counselling, anticipating realistic trajectories, and informing practical decision making for families and clinicians involved. Many families in the reverse phenotyping studies had no history of targeted clinical care to address symptomatology, emphasising the weight of this work. The results of this thesis, alongside continued speech and language phenotyping going forward, will provide increased clinical precision, and an understanding of the interplay between chromatin genes, neural development, and communication. The consequences of this research will help to identify useful biomarkers for the growing field of postnatal modification of epigenetic marks.
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ItemDevelopment and validation of the short language measure (SLaM): a brief measure of general language ability for children in their first year at school( 2018)The identification of children with language difficulties relies on the referral of children to speech-language services. Yet, the referrers of young school-aged children cannot always accurately discriminate those with and without language difficulties. Consequently, a high proportion of children with language difficulties are never referred for services and many children referred for suspected language difficulties have age-appropriate communication skills. The administration of a short language measure by speech-language therapists or paraprofessionals to identify children who require further language evaluation could improve the accuracy of language service referrals. However, existing short language measures for young school-aged children lack sufficient discrimination capacity. This may be due to the inadequate development of available measures, which have omitted crucial test development steps. The aim of this project was to create a sufficiently accurate, valid and reliable short language measure for children in their first year at school by applying stringent test development procedures.
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ItemSpeech and language phenotyping in children with cleft lip and/or palate and their unaffected relatives( 2019)Background: Cleft lip and/or palate (CL/P) is one of the most common birth defects. Non-syndromic CL/Ps make up 70% of cases and are associated with complex phenotypes, challenging accurate clinical diagnosis and prognostication. Children with CL/P may have impaired language, or disordered speech associated with velopharyngeal insufficiency (VPI). Existing research defines several sub-clinical cleft phenotypes, identified from unaffected relatives, that may advance clinical knowledge and contribute to our understanding of genetic aetiology. VPI has long been suggested as a sub-clinical phenotype, but only recently studied. Aims: Broad aims were: (1) to systematically review the literature exploring speech and language skills of children with submucous cleft palate (SMCP); (2) to describe the speech and language characteristics of probands with different cleft types; and (3) to provide sub-clinical speech phenotyping for clinically ‘unaffected’ relatives of probands with cleft lip with or without palate (CL±P). Methods: (1) Five databases were comprehensively searched. Included studies reported speech or language profiles of individuals with SMCP. (2) Participants with clefts (overt CL/P n = 37; SMCP n = 15) were recruited from the cleft registry at the Royal Children’s Hospital (RCH), Melbourne, Australia. Language data from non-cleft participants was obtained from the Early Language in Victoria Study (n = 129). (3) Probands with overt clefts were identified from the RCH cleft registry, and their unaffected family members were contacted for participation (n = 189). Non-cleft participants were recruited from Melbourne, Australia (n = 207). All participants had non-syndromic diagnoses with no medical conditions likely to impact communication. Non-cleft participants also had no known family history of clefting. Speech was assessed perceptually, using common clinical tools, and instrumentally with the Nasometer. Language was assessed using the Clinical Evaluation of Language Fundamentals, Fourth Edition and the Children’s Communication Checklist, Second Edition. Non-verbal IQ was screened using the Weschler Abbreviated Scale of Intelligence, Second Edition. Results: (1) Children with SMCP may present with speech difficulties similar to those experienced by individuals with overt clefts. There is a dearth of literature exploring the language abilities of this population. (2) Children with overt clefts had language skills that were comparable to their non-cleft peers. Those with SMCP had variable speech and language performance, with overall poorer language than those with or without overt clefts. Participants with SMCP and poor language also had low non-verbal IQ. (3) Speech in unaffected relatives was not significantly different to that of a matched non-cleft cohort. Discussion & conclusion: Detailed phenotyping from this thesis highlights a diversity in communication profiles between and within groups of individuals with different cleft types. Results emphasise the importance of individualised assessment, where clinicians do not make assumptions based on a child’s cleft. Conclusions from the SMCP study suggest that other unidentified neurodevelopmental disorders may be present, questioning the accuracy of truly ‘non-syndromic’ diagnoses. Data from the third aim suggest that VPI is not a significant sub-clinical phenotype of non-syndromic CL±P and thus may not warrant further exploration in familial genetic investigations. Outcomes contribute to the complex CL/P phenotyping and genotyping landscape.
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ItemEarly feeding and communication skills in children born at <30 weeks of gestational age( 2018)Introduction Children born preterm are at risk of adverse neurodevelopment, potentially including disordered feeding, voice, speech, and language. The literature lacks an integrated picture of these domains, and predictors are uncertain, though preliminary evidence suggests that oromotor feeding may predict voice, speech, and language. This study had the following aims, addressed at various times across three waves of data collection at 12, 24, and 36 months of age: 1. To characterise the feeding abilities of children born at <30 weeks of gestational age in comparison with children born at term 2. To determine significant predictors of feeding ability in children born at <30 weeks of gestational age 3. To characterise the voice, speech, and language abilities of children born at <30 weeks of gestational age in comparison with children born at term 4. To determine significant predictors of voice, speech, and language ability in children born at <30 weeks of gestational age; and a. In particular to evaluate early feeding abilities as a predictor of later voice, speech, and language abilities Methods Within two weeks of birth, 149 children born <30 weeks’ gestational age, and 151 term-born children were recruited from the Royal Women’s Hospital. At 12 months’, the Schedule for Oromotor Assessment (SOMA) was administered. At 24 months’, the Communication and Symbolic Behavior Scales–Infant Toddler Profile, and Bayley Scales of Infant-Todder Development–3rd Edition were administered. At 36 months’, the Behavioral Pediatrics Feeding Assessment Scale, the Pediatric Voice Handicap Index, the Grade, Roughness, Breathiness, Asthenia, Strain Scale, the Diagnostic Evaluation of Articulation and Phonology and the Preschool Language Scales—5th Edition were administered. Outcomes were compared between groups, and potential predictors were analysed. Results Children born <30 weeks’ performed worse than term-born peers at oromotor feeding at 12 months’, language at 24 months’, and language at 36 months’. Voice, speech, and feeding behaviour at 36 months’ were similar between groups. Oromotor feeding at 12 months’ was predicted (p<0.05) by infant neurobehaviour, brain biparietal diameter on Magnetic Resonance Imaging (MRI), and neonatal surgery; but not by other MRI metrics (e.g. white matter score), sex, gestational age at birth (GA), birth-weight, social risk, tube feeding, or respiratory support. Language at 24 months’ was predicted (p<0.05) by sex, GA, hearing loss, and multilingualism; but not birth-weight, maternal education, neonatal brain abnormality, medical risk, or early feeding. Language at 36 months’ was predicted (p<0.05) by sex, neurodevelopmental disorder, and high social risk; but not GA, birth-weight, chronic lung disease, multilingualism, or early feeding. Voice at 36 months’ was predicted (p<0.05) only by chronic lung disease; speech at 36 months’ was not predicted by any hypothesised risk factors. Conclusion Oromotor feeding at 12 months’, and language across the early years were concerns for children born at <30 weeks’ GA. Speech and voice were not affected, contrary to previous reports. Predictors reported in this study may be used to identify those children at greatest risk of adverse outcomes, facilitating surveillance and timely intervention.
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ItemMild and moderate congenital hearing loss in childhood: trends and associations with language outcomes( 2018)Background: Children born with mild and moderate bilateral hearing loss experience poorer language outcomes than peers without hearing loss. Following implementation of universal newborn hearing screening (UNHS) in the early 2000s, most children are now fitted with hearing aids very early, even without firm evidence of efficacy. Filling this knowledge gap would support clinicians and families to make appropriate decisions for affected children. Aims: In population-based samples of children born with mild and moderate bilateral hearing loss in two age groups, I aimed to describe the: 1) language and child wellbeing outcomes at 5-8 years of age examined both by system of hearing loss detection and age at detection; 2) relationship between measures of hearing ability (aided and unaided) and speech/language outcomes at 5-7 years of age; and 3) expressive vocabulary of children at age 1-3 years, with comparison to same-aged children without hearing loss. Methods: All participants were drawn from population-based studies or databanks with comparable measures and demographic composition in Victoria and New South Wales. In Aim 1, 21 directly assessed children (5-7 years) were analysed with 125 children (5-8 years) from historical hearing loss cohorts and 1217 children (7 years) without known hearing loss. For Aim 2, hearing aid data were obtained for 19 directly assessed children. In Aim 3, questionnaire data were compared between 20 children (1-3 years) with and 1711 children (2 years) without known hearing loss. Language was assessed or parent-reported, with additional data collected by parent questionnaire. Aim 1 was analysed using unadjusted and adjusted regression models, with potential confounders identified a priori. For Aims 2 and 3, analyses were descriptive and exploratory. Results: Outcomes for 5-7 year olds with moderate loss improved across detection systems spanning opportunistic through to UNHS (mean expressive language p for trend .05, receptive vocabulary p for trend .06) and were better when diagnosed before age 6 months. Children with mild loss did not show similar benefit, despite trends toward earlier diagnosis and hearing aid fitting. Children with mild-moderate loss had poorer expressive language than children without loss (adjusted mean difference -8.9 points, 95% CI -14.7 to -3.1). Audibility measures correlated with unaided hearing (r=-.60 to -.79, p=.02 to <.001) and speech recognition ability (r=-.63 to -.73, p=.04 to .01). Unaided and aided hearing measures did not show associations with speech and language. On average 1-3 year olds with, versus without, hearing loss had lower expressive vocabulary raw scores even though older at assessment. Language of children with mild loss was on average 9 months behind expectations (SD 5.6 months), moderate loss on average 6.6 months behind (SD 6.7 months). Conclusions: Children with mild and moderate hearing loss show early language delays that persist into primary school. Children with moderate loss showed some benefit from earlier detection and fitting with hearing aids. Children with mild loss did not, which is concerning given the current practice of earlier hearing aid fitting. A population-based trial of hearing aids for mild losses would clarify the benefits versus costs of this approach.
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ItemLanguage development in autism spectrum disorder: longitudinal comparison with a community cohort of children with language impairment and typical development( 2016)Background: Autism spectrum disorder (ASD) is a lifelong developmental disability that affects more than 1 in 50 children in Australia. Language difficulties are common in ASD with up to 30% of children unable to communicate using words. Despite a substantial number of studies examining language outcomes in individuals with ASD, it is difficult for families and clinicians to interpret study findings. This is because many studies use; selected clinical samples that may not generalise to the broader population, heterogeneous methodology, and the quality of studies varies. Rarely do studies use standardised language-specific tools. In addition, few studies have compared development in children with ASD to children without ASD, which means it is difficult to place differences in children with ASD within a developmental context. As a consequence, we do not yet fully understand how language develops in children with ASD and we are not able to accurately predict language outcomes. Parents and clinicians need evidence about language trajectories in ASD to inform decision-making and understand prognosis. Service providers and policy makers also require information for appropriate resource allocation for current and future needs. Aims: The overall aim of this thesis was to examine trajectories of language development in individuals diagnosed with ASD. To achieve this aim, three main studies were conducted. Study 1 systematically reviewed and synthesised the extant literature on language outcomes in individuals with ASD. Studies 2 and 3 examined individual and mean trajectories of language development in children with ASD from 1 to 2 years and 4 to 7 years, respectively, and compared these trajectories to large samples of children with language impairment (LI) and typical language development (TD). Study 3 described language trajectories for children with ASD and investigated predictors of language outcomes from 4 to 7 years in children with and without ASD. Method: Children in studies 2 and 3 were recruited from a prospective longitudinal community-based study of 1910 children in Victoria (the Early Language in Victoria Study; ELVS). Individual and mean trajectories were mapped from 1 to 2 years (ASD; n=41, LI: n=119, TD: n=861) and 4 to 7 years (ASD; n=27, LI n=110, TD: n=831). In Study 2, individual and mean communication trajectories were mapped using scores from two parent checklists, namely the Communication Symbolic Behaviour Scales Infant Toddler Checklist and the MacArthur Bates Communicative Development Inventories. We compared the proportion of children who lost specific communication skills between the three groups (ASD, LI, TD) and the spread of loss across different communication domains. In Study 3 we used the Clinical Evaluation of Language Fundamentals data collected in ELVS (preschool second edition and fourth edition) to map individual and mean language trajectories from 4 to 7 years. The proportion of children who had declined, remained stable or accelerated in language skills was compared across groups. Putative predictors of language outcomes were also investigated. Results: Language ability was heterogeneous, however, mean scores for children with ASD and LI were lower than scores for children with TD and reference norms, in all studies included in the systematic review and Studies 2 and 3 in the community sample. From 1 to 2 years, the gap between children with ASD and TD/LI grew larger in all communication domains except in the areas of speech and expressive vocabulary, which was similar for children with LI and ASD. From 4-7 years, despite having lower language ability on average compared with the typically developing group, most children with ASD were developing language at the same pace as the LI and TD children. A diagnosis of ASD did not predict a greater gap between receptive and expressive language ability. The child’s early language ability and IQ were most important in predicting language ability at a later age. Conclusion: Systematic review and synthesis of existing studies showed that children with ASD in all studies (with one exception) had lower scores at baseline when compared with reference norms but children tracked in parallel to reference norms. The limited amount of data available from studies investigating children over 9 years made it difficult to draw accurate conclusions on trajectories beyond this age, however the few studies that had presented data suggest rate of language progress may slow from around 10 years. In Studies 2 and 3 that utilised the ELVS, children with ASD demonstrated communication abilities that were not significantly different to other children at12 months of age in most areas. However, on average their language and social communication progressed at a slower rate than other children from around 12 months to 2 years in most areas of communication. Findings from children in the ELVS aged 4 to 7 years were consistent with the systematic review findings. In Study 3 children with ASD who were verbal and had IQ in the normal range demonstrated lower language scores at baseline and follow up on average, but tracked in parallel to reference norms over time. The knowledge gained from this thesis will help guide prognostic information to be provided to parents. It will also assist with planning for future support needs of individuals with ASD.