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Item does not contain fulltext Speech and language impairment is core in Koolen-de Vries syndrome (KdVS), yet only one study has examined this empirically. Here we define speech, language, and functional/adaptive behaviour in KdVS; while deeply characterising the medical/neurodevelopmental phenotype in the largest cohort to date. Speech, language, literacy, and social skills were assessed using standardised measures, alongside an in-depth health and medical questionnaire. 81 individuals with KdVS were recruited (35 female, mean age 9y 10mo), 56 of whom harboured the typical 500-650 kb 17q21.31 deletion. The core medical phenotype was intellectual disability (largely moderate), eye anomalies/vision disturbances, structural brain anomalies, dental problems, sleep disturbance, musculoskeletal abnormalities, and cardiac defects. Most were verbal (62/81, 76.5%), while minimally-verbal communicators used alternative and augmentative communication (AAC) successfully in spite of speech production delays. Speech was characterised by apraxia (39/61, 63.9%) and dysarthria (28/61, 45.9%) in verbal participants. Stuttering was described in 36/47 (76.6%) verbal participants and followed a unique trajectory of late onset and fluctuating presence. Receptive and expressive language abilities were commensurate with one another, but literacy skills remained a relative weakness. Social competence, successful behavioural/emotional control, and coping skills were areas of relative strength, while communication difficulties impacted daily living skills as an area of comparative difficulty. Notably, KdVS individuals make communication gains beyond childhood and should continue to access targeted therapies throughout development, including early AAC implementation, motor speech therapy, language/literacy intervention, as well as strategies implemented to successfully navigate activities of daily living that rely on effective communication.

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Childhood apraxia of speech (CAS), the prototypic severe childhood speech disorder, is characterized by motor programming and planning deficits. Genetic factors make substantive contributions to CAS aetiology, with a monogenic pathogenic variant identified in a third of cases, implicating around 20 single genes to date. Here we ascertained 70 unrelated probands with a clinical diagnosis of CAS and performed trio genome sequencing. Our bioinformatic analysis examined single nucleotide, indel, copy number, structural and short tandem repeat variants. We prioritised appropriate variants arising de novo or inherited that were expected to be damaging based on in silico predictions. We identified high confidence variants in 18/70 (26%) probands, almost doubling the current number of candidate genes for CAS. Three of the 18 variants affected SETBP1, SETD1A and DDX3X, thus confirming their roles in CAS, while the remaining 15 occurred in genes not previously associated with this disorder. Fifteen variants arose de novo and three were inherited. We provide further novel insights into the biology of child speech disorder, highlighting the roles of chromatin organization and gene regulation in CAS, and confirm that genes involved in CAS are co-expressed during brain development. Our findings confirm a diagnostic yield comparable to, or even higher, than other neurodevelopmental disorders with substantial de novo variant burden. Data also support the increasingly recognised overlaps between genes conferring risk for a range of neurodevelopmental disorders. Understanding the aetiological basis of CAS is critical to end the diagnostic odyssey and ensure affected individuals are poised for precision medicine trials.

Language is foundational for neurodevelopment and quality of life, but an estimated 10% of children have a language disorder at age 5. Many children shift between classifications of typical and low language if assessed at multiple times in the early years, making it difficult to identify which children will have persisting difficulties and benefit most from support. This study aims to identify a parsimonious set of preschool indicators that predict language outcomes in late childhood, using data from the population-based Early Language in Victoria Study (n = 839).Parents completed surveys about their children at ages 8, 12, 24, and 36 months. At 11 years, children were assessed using the Clinical Evaluation of Language Fundamentals 4th Edition (CELF-4). We used random forests to identify which of the 1990 parent-reported questions best predict children's 11-year language outcome (CELF-4 score ≤81 representing low language) and used SuperLearner to estimate the accuracy of the constrained sets of questions.At 24 months, seven predictors relating to vocabulary, symbolic play, pragmatics and motor skills yielded 73% sensitivity (95% CI: 57, 85) and 77% specificity (95% CI: 74, 80) for predicting low language at 11 years. At 36 months, 7 predictors relating to morphosyntax, vocabulary, parent-child interactions, and parental stress yielded 75% sensitivity (95% CI: 58, 88) and 85% specificity (95% CI: 81, 87). Measures at 8 and 12 months yielded unsatisfactory accuracy.We identified two short sets of questions that predict language outcomes at age 11 with fair accuracy. Future research should seek to replicate results in a separate cohort.

An expanding range of genetic syndromes are characterized by genome-wide disruptions in DNA methylation profiles referred to as episignatures. Episignatures are distinct, highly sensitive and specific biomarkers that have recently been applied in clinical diagnosis of genetic syndromes. Episignatures are contained within the broader disorder-specific genome-wide DNA methylation changes which can share significant overlap amongst different conditions. In this study we performed functional genomic assessment and comparison of disorder-specific and overlapping genome-wide DNA methylation changes related to 65 genetic syndromes with previously described episignatures. We demonstrate evidence of disorder-specific and recurring genome-wide differentially methylated probes (DMPs) and regions (DMRs). The overall distribution of DMPs and DMRs across the majority of the neurodevelopmental genetic syndromes analyzed showed substantial enrichment in gene promoters and CpG islands, and under-representation of the more variable intergenic regions. Analysis showed significant enrichment of the DMPs and DMRs in gene pathways and processes related to neurodevelopment, including neurogenesis, synaptic signaling and synaptic transmission. This study expands beyond the diagnostic utility of DNA methylation episignatures by demonstrating correlation between the function of the mutated genes and the consequent genomic DNA methylation profiles as a key functional element in the molecular etiology of genetic neurodevelopmental disorders. This article is protected by copyright. All rights reserved.

Current methods for reporting interventions do not allow key questions of importance to practitioners, service providers, policy-makers and people with DLD to be answered, and hence limit the implementation of effective interventions in the real world. To extend the existing EQUATOR guidelines to the context of speech language therapy/pathology for children with language disorder and to provide more specific guidance on participants, interventions and outcomes within the CONSORT checklist (used to improve the reporting of randomised controlled trials) and TIDieR (Template for Intervention Description and Replication) to ensure consistency of reporting. We will develop a core team to include representatives from each of the key groups who will either use or be influenced by the final reporting guidance across different countries. To achieve each set of aims, we will conduct reviews of the literature (which present typologies of intervention characteristics in (D)LD and related disorders); carry out focus groups; and use systematic consensus methods such as the Delphi technique, nominal group technique or consensus development conferences. Through the development and adoption of standard intervention reporting criteria, we anticipate that we will overcome the numerous barriers for practitioners, services and policy-makers in applying intervention evidence to practice. We believe that establishing international consensus on reporting guidelines would significantly accelerate progress in DLD research and the ease with which it can be used in clinical practice, by capitalising on the growth in intervention studies to enable international collaboration and new methodologies of data pooling, meta-analyses and cross-study comparisons.

Speech and language impairment is core in Koolen-de Vries syndrome (KdVS), yet only one study has examined this empirically. Here we define speech, language, and functional/adaptive behaviour in KdVS; while deeply characterising the medical/neurodevelopmental phenotype in the largest cohort to date. Speech, language, literacy, and social skills were assessed using standardised measures, alongside an in-depth health and medical questionnaire. 81 individuals with KdVS were recruited (35 female, mean age 9y 10mo), 56 of whom harboured the typical 500-650 kb 17q21.31 deletion. The core medical phenotype was intellectual disability (largely moderate), eye anomalies/vision disturbances, structural brain anomalies, dental problems, sleep disturbance, musculoskeletal abnormalities, and cardiac defects. Most were verbal (62/81, 76.5%), while minimally-verbal communicators used alternative and augmentative communication (AAC) successfully in spite of speech production delays. Speech was characterised by apraxia (39/61, 63.9%) and dysarthria (28/61, 45.9%) in verbal participants. Stuttering was described in 36/47 (76.6%) verbal participants and followed a unique trajectory of late onset and fluctuating presence. Receptive and expressive language abilities were commensurate with one another, but literacy skills remained a relative weakness. Social competence, successful behavioural/emotional control, and coping skills were areas of relative strength, while communication difficulties impacted daily living skills as an area of comparative difficulty. Notably, KdVS individuals make communication gains beyond childhood and should continue to access targeted therapies throughout development, including early AAC implementation, motor speech therapy, language/literacy intervention, as well as strategies implemented to successfully navigate activities of daily living that rely on effective communication.

ObjectiveTo determine whether specific speech, language, and oromotor profiles are associated with different patterns of polymicrogyria, we assessed 52 patients with polymicrogyria using a battery of standardized tests and correlated findings with topography and severity of polymicrogyria.MethodsPatients were identified via clinical research databases and invited to participate, irrespective of cognitive and verbal language abilities. We conducted standardized assessments of speech, oromotor structure and function, language, and nonverbal IQ. Data were analyzed according to normative assessment data and descriptive statistics. We conducted a correlation analysis between topographic pattern and speech and language findings.ResultsFifty-two patients (33 male, 63%) were studied at an average age of 12.7 years (range 2.5–36 years). All patients had dysarthria, which ranged from mild impairment to anarthria. Developmental speech errors (articulation and phonology), oral motor structure and function deficits, and language disorder were frequent. A total of 23/29 (79%) had cognitive abilities in the low average to extremely low range. In the perisylvian polymicrogyria group (36/52), speech, everyday language, and oral motor impairments were more severe, compared to generalized (1 patient), frontal (3), polymicrogyria with periventricular nodular heterotopia (3), parasagittal parieto-occipital (1), mesial occipital (1), and other (7) patterns.ConclusionsDysarthria is a core feature of polymicrogyria, often accompanied by receptive and expressive language impairments. These features are associated with all polymicrogyria distribution patterns and more severe in individuals with bilateral polymicrogyria, particularly in the perisylvian region.

Heterozygous pathogenic WAC variants cause Desanto-Shinawi syndrome; affected patients have dysmorphic features, developmental impairment and behavioral abnormalities. Seizures are reported in one quarter, including tonic-clonic, absence, and febrile seizures. This study aimed to better understand the phenotypic spectrum of epilepsy and development in Desanto-Shinawi syndrome. We identified four children with seizures and pathogenic WAC variants, including two siblings. All had global developmental impairment with language affected most severely; two had diagnoses of childhood apraxia of speech and two had autism spectrum disorder. Seizure onset age ranged from six months to 14 years. Seizures always occurred from sleep and were focal impaired awareness with motor features in three patients, with one having bilateral tonic-clonic seizures of suspected focal onset. Two patients had spontaneous seizure resolution without treatment, and the remaining two were well-controlled on monotherapy. EEG was normal in two patients; one had focal right frontal spikes in drowsiness and sleep while the last had independent centrotemporal spikes from both hemispheres, activated in sleep. All patients had heterozygous truncating pathogenic WAC variants, with negative parental testing. The findings in this cohort of patients suggest that epilepsy in Desanto-Shinawi syndrome is usually focal and self-limited, and may fall within the epilepsy-aphasia spectrum.

Item does not contain fulltext SETBP1 haploinsufficiency disorder (MIM#616078) is caused by haploinsufficiency of SETBP1 on chromosome 18q12.3, but there has not yet been any systematic evaluation of the major features of this monogenic syndrome, assessing penetrance and expressivity. We describe the first comprehensive study to delineate the associated clinical phenotype, with findings from 34 individuals, including 24 novel cases, all of whom have a SETBP1 loss-of-function variant or single (coding) gene deletion, confirmed by molecular diagnostics. The most commonly reported clinical features included mild motor developmental delay, speech impairment, intellectual disability, hypotonia, vision impairment, attention/concentration deficits, and hyperactivity. Although there is a mild overlap in certain facial features, the disorder does not lead to a distinctive recognizable facial gestalt. As well as providing insight into the clinical spectrum of SETBP1 haploinsufficiency disorder, this reports puts forward care recommendations for patient management.

Heterozygous disruptions ofHere we phenotyped 28 individuals from 17 families with pathogenicSpeech disorders were prevalent (23/25, 92%) and CAS was most common (22/25, 88%), with similar speech presentations across English and German. Speech was still impaired in adulthood, and some speech sounds (eg, 'th', 'r', 'ch', 'j') were never acquired. Language impairments (21/25, 84%) ranged from mild to severe. Comorbidities included feeding difficulties in infancy (10/27, 37%), fine (13/26, 50%) and gross (13/26, 50%) motor impairment, anxiety (5/27, 19%), depression (6/27, 22%) and sleep disturbance (11/15, 44%). Physical features were common (22/27, 81%) but with no consistent pattern. Cognition ranged from average to mildly impaired and was incongruent with language ability; for example, seven participants with severe language disorder had average non-verbal cognition.Although we identify an increased prevalence of conditions like anxiety, depression and sleep disturbance, we confirm that the consequences of

ObjectiveDetermining 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).MethodsPrecise 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.ResultsThirty-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.ConclusionWe 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.

Germline de novo SETBP1 variants cause clinically distinct and heterogeneous neurodevelopmental disorders. Heterozygous missense variants at a hotspot encoding a canonical degron lead to SETBP1 accumulation and Schinzel-Giedion syndrome (SGS), a rare severe developmental disorder involving multisystem malformations. Heterozygous loss-of-function variants result in SETBP1 haploinsufficiency disorder which is phenotypically much milder than SGS. Following an initial description of four individuals with atypical SGS carrying heterozygous missense variants adjacent to the degron, a few individual cases of variants outside the degron were reported. Due to the lack of systematic investigation of genotype-phenotype associations of different types of SETBP1 variants, and limited understanding of the roles of the gene in brain development, the extent of clinical heterogeneity and how this relates to underlying pathophysiological mechanisms remain elusive, imposing challenges for diagnosis and patient care. Here, we present a comprehensive investigation of the largest cohort to-date of individuals carrying SETBP1 missense variants outside the degron (n=18, including one in-frame deletion). We performed thorough clinical and speech phenotyping with functional follow-up using cellular assays and transcriptomics. Our findings suggest that such variants cause a clinically and functionally variable developmental syndrome, showing only partial overlaps with classical SGS and SETBP1 haploinsufficiency disorder, and primarily characterised by intellectual disability, epilepsy, speech and motor impairment. We provide evidence of loss-of-function pathophysiological mechanisms impairing ubiquitination, DNA-binding and transcription. In contrast to SGS and SETBP1 haploinsufficiency, these effects are independent of protein abundance. Overall, our study provides important novel insights into diagnosis, patient care and aetiology of SETBP1-related disorders.

To examine the phenomenology of stuttering across the lifespan in the largest prospective cohort to date.Participants aged 7 years and older with a history of developmental stuttering were recruited. Self-reported phenotypic data were collected online including stuttering symptomatology, co-occurring phenotypes, genetic predisposition, factors associated with stuttering severity, and impact on anxiety, education, and employment.A total of 987 participants (852 adults: 590 males, 262 females, mean age 49 years [SD = 17 years 10 months; range = 18-93 years] and 135 children: 97 males, 38 females, mean age 11 years 4 months [SD = 3 years; range = 7-17 years]) were recruited. Stuttering onset occurred at age 3 to 6 years in 64.0%. Blocking (73.2%) was the most frequent phenotype; 75.9% had sought stuttering therapy and 15.5% identified as having recovered. Half (49.9%) reported a family history. There was a significant negative correlation with age for both stuttering frequency and severity in adults. Most were anxious due to stuttering (90.4%) and perceived stuttering as a barrier to education and employment outcomes (80.7%).The frequent persistence of stuttering and the high proportion with a family history suggest that stuttering is a complex trait that does not often resolve, even with therapy. These data provide new insights into the phenotype and prognosis of stuttering, information that is critically needed to encourage the development of more effective speech therapies.Half of the study cohort had a family history of stuttering. While 75.9% of participants had sought stuttering therapy, only 15.5% identified as having recovered. There was a significant negative correlation between age and stuttering frequency and severity in adults.

Background and aims Developmental motor speech impairment has been suspected, but rarely systematically examined, in low- and minimally verbal individuals with autism spectrum disorder. We aimed to investigate the extent of motor speech impairment in this population and its relation to number of different words produced during a semi-structured language sample. Methods Videos of 54 low-verbal and minimally verbal individuals (ages 4;4–18;10) performing portions of a speech praxis test were coded for signs of motor speech impairment (e.g., childhood apraxia of speech). Age, autism spectrum disorder severity, nonspeech oral-motor ability, speech production ability, nonverbal IQ, and receptive vocabulary were compared between groups. Results Four groups emerged: (1) speech within normal limits ( n = 12), (2) non-childhood apraxia of speech impairment ( n = 16), (3) suspected childhood apraxia of speech ( n = 13), and (4) insufficient speech to rate ( n = 13). Groups differed significantly in nonspeech oral-motor ability, speech production ability, nonverbal IQ, and receptive vocabulary. Overall, only speech production ability and receptive vocabulary accounted for significant variance in number of different words. Receptive vocabulary significantly predicted number of different words only in Groups 1 and 2, while speech production ability significantly predicted number of different words only in Groups 3 and 4. Conclusions and implications If replicated, our findings have important implications for developing much-needed spoken language interventions in minimally verbal individuals with autism spectrum disorder.

Item does not contain fulltext Speech and language impairments are commonly reported in DYRK1A syndrome. Yet, speech and language abilities have not been systematically examined in a prospective cohort study. Speech, language, social behaviour, feeding, and non-verbal communication skills were assessed using standardised tools. The broader health and medical phenotype was documented using caregiver questionnaires, interviews and confirmation with medical records. 38 individuals with DYRK1A syndrome (23 male, median age 8 years 3 months, range 1 year 7 months to 25 years) were recruited. Moderate to severe intellectual disability (ID), autism spectrum disorder (ASD), vision, motor and feeding impairments were common, alongside epilepsy in a third of cases. Speech and language was disordered in all participants. Many acquired some degree of verbal communication, yet few (8/38) developed sufficient oral language skills to rely solely on verbal communication. Speech was characterised by severe apraxia and dysarthria in verbal participants, resulting in markedly poor intelligibility. Those with limited verbal language (30/38) used a combination of sign and graphic augmentative and alternative communication (AAC) systems. Language skills were low across expressive, receptive, and written domains. Most had impaired social behaviours (25/29). Restricted and repetitive interests were most impaired, whilst social motivation was a relative strength. Few individuals with DYRK1A syndrome use verbal speech as their sole means of communication, and hence, all individuals need early access to tailored, graphic AAC systems to support their communication. For those who develop verbal speech, targeted therapy for apraxia and dysarthria should be considered to improve intelligibility and, consequently, communication autonomy.

Language disorders are highly heritable and are influenced by complex interactions between genetic and environmental factors. Despite more than twenty years of research, we still lack critical understanding of the biological underpinnings of language. This review provides an overview of the genetic landscape of developmental language disorders (DLD), with an emphasis on the importance of defining the specific features (the phenotype) of DLD to inform gene discovery. We review the specific phenotype of DLD in the genetic literature, and the influence of historic variation in diagnostic inclusion criteria on researchers’ ability to compare and replicate genotype–phenotype studies. This review provides an overview of the recently identified gene pathways in populations with DLD and explores current state-of-the-art approaches to genetic analysis based on the hypothesised architecture of DLD. We will show how recent global efforts to unify diagnostic criteria have vastly increased sample size and allow for large multi-cohort metanalyses, leading the identification of a growing number of contributory loci. We emphasise the important role of estimating the genetic architecture of DLD to decipher underlying genetic associations. Finally, we explore the potential for epigenetics and environmental interactions to further unravel the biological basis of language disorders.

Summary: Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes. We demonstrate increasing resolution and specificity ranging from protein complex, gene, sub-gene, protein domain, and even single nucleotide-level Mendelian episignatures. We show the power of multiclass modeling to develop highly accurate and disease-specific diagnostic classifiers. This study significantly expands the number and spectrum of disorders with detectable DNA methylation episignatures, improves the clinical diagnostic capabilities through the resolution of unsolved cases and the reclassification of variants of unknown clinical significance, and provides further insight into the molecular etiology of Mendelian conditions.

Neurodevelopmental disorders are highly heterogenous conditions resulting from abnormalities of brain architecture and/or function. FBXW7 (F-box and WD-repeat-domain-containing 7), a recognized developmental regulator and tumor suppressor, has been shown to regulate cell-cycle progression and cell growth and survival by targeting substrates including CYCLIN E1/2 and NOTCH for degradation via the ubiquitin proteasome system. We used a genotype-first approach and global data-sharing platforms to identify 35 individuals harboring de novo and inherited FBXW7 germline monoallelic chromosomal deletions and nonsense, frameshift, splice-site, and missense variants associated with a neurodevelopmental syndrome. The FBXW7 neurodevelopmental syndrome is distinguished by global developmental delay, borderline to severe intellectual disability, hypotonia, and gastrointestinal issues. Brain imaging detailed variable underlying structural abnormalities affecting the cerebellum, corpus collosum, and white matter. A crystal-structure model of FBXW7 predicted that missense variants were clustered at the substrate-binding surface of the WD40 domain and that these might reduce FBXW7 substrate binding affinity. Expression of recombinant FBXW7 missense variants in cultured cells demonstrated impaired CYCLIN E1 and CYCLIN E2 turnover. Pan-neuronal knockdown of the Drosophila ortholog, archipelago, impaired learning and neuronal function. Collectively, the data presented herein provide compelling evidence of an F-Box protein-related, phenotypically variable neurodevelopmental disorder associated with monoallelic variants in FBXW7.

Developmental stuttering is a condition of speech dysfluency, characterized by pauses, blocks, prolongations and sound or syllable repetitions. It affects around 1% of the population, with potential detrimental effects on mental health and long-term employment. Accumulating evidence points to a genetic aetiology, yet gene–brain associations remain poorly understood due to a lack of MRI studies in affected families. Here we report the first neuroimaging study of developmental stuttering in a family with autosomal dominant inheritance of persistent stuttering. We studied a four-generation family, 16 family members were included in genotyping analysis. T1-weighted and diffusion-weighted MRI scans were conducted on seven family members (six male; aged 9–63 years) with two age and sex matched controls without stuttering (n = 14). Using Freesurfer, we analysed cortical morphology (cortical thickness, surface area and local gyrification index) and basal ganglia volumes. White matter integrity in key speech and language tracts (i.e. frontal aslant tract and arcuate fasciculus) was also analysed using MRtrix and probabilistic tractography. We identified a significant age by group interaction effect for cortical thickness in the left hemisphere pars opercularis (Broca’s area). In affected family members this region failed to follow the typical trajectory of age-related thinning observed in controls. Surface area analysis revealed the middle frontal gyrus region was reduced bilaterally in the family (all cortical morphometry significance levels set at a vertex-wise threshold of P < 0.01, corrected for multiple comparisons). Both the left and right globus pallidus were larger in the family than in the control group (left P = 0.017; right P = 0.037), and a larger right globus pallidus was associated with more severe stuttering (rho = 0.86, P = 0.01). No white matter differences were identified. Genotyping identified novel loci on chromosomes 1 and 4 that map with the stuttering phenotype. Our findings denote disruption within the cortico-basal ganglia-thalamo-cortical network. The lack of typical development of these structures reflects the anatomical basis of the abnormal inhibitory control network between Broca’s area and the striatum underpinning stuttering in these individuals. This is the first evidence of a neural phenotype in a family with an autosomal dominantly inherited stuttering.

The use of spoken and written language is a capacity that is unique to humans. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30-80%, depending on the trait. The relevant genetic architecture is complex, heterogeneous, and multifactorial, and yet to be investigated with well-powered studies. Here, we present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures: word reading, nonword reading, spelling, phoneme awareness, and nonword repetition, with total sample sizes ranging from 13,633 to 33,959 participants aged 5-26 years (12,411 to 27,180 for those with European ancestry, defined by principal component analyses). We identified a genome-wide significant association with word reading (rs11208009, p=1.098 × 10−8) independent of known loci associated with intelligence or educational attainment. All five reading-/language-related traits had robust SNP-heritability estimates (0.13–0.26), and genetic correlations between them were modest to high. Using genomic structural equation modelling, we found evidence for a shared genetic factor explaining the majority of variation in word and nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence and educational attainment. A multivariate GWAS was performed to jointly analyse word and nonword reading, spelling, and phoneme awareness, maximizing power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with neuroimaging traits identified association with cortical surface area of the banks of the left superior temporal sulcus, a brain region with known links to processing of spoken and written language. Analysis of evolutionary annotations on the lineage that led to modern humans showed enriched heritability in regions depleted of Neanderthal variants. Together, these results provide new avenues for deciphering the biological underpinnings of these uniquely human traits.

Importance: Cerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years. Objective: To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support. Evidence Review: The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. Findings: Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent support (5). Conclusions and Relevance: When a child meets the criteria of high risk of CP, intervention should start as soon as possible. Parents want an early diagnosis and treatment and support implementation as soon as possible. Early intervention builds on a critical developmental time for plasticity of developing systems. Referrals for intervention across the 9 domains should be specific as per recommendations in this guideline.

Here, a moral case is presented as to why sign languages such as Auslan should be made compulsory in general school curricula. Firstly, there are significant benefits that accrue to individuals from learning sign language. Secondly, sign language education is a matter of justice; the normalisation of sign language education and use would particularly benefit marginalised groups, such as those living with a communication disability. Finally, the integration of sign languages into the curricula would enable the flourishing of Deaf culture and go some way to resolving the tensions that have arisen from the promotion of oralist education facilitated by technologies such as cochlear implants. There are important reasons to further pursue policy proposals regarding the prioritisation of sign language in school curricula.

Despite the widespread use of nonword repetition in child neuropsychological research and clinical practice, the specific cognitive, linguistic and motor processes that contribute to variability in performance are unclear. The aim of this work was to determine the role of phonological memory, word reading, oromotor sequencing, and oromotor control on nonword repetition performance in the context of children’s speech and language abilities. Ninety one children between the ages of 9 and 11 years, with a broad range of speech and language abilities participated in the study. Hierarchical regression was used to a) evaluate the contribution of phonological memory, word reading, oromotor sequencing and oromotor control to nonword repetition and b) determine whether speech and/or language ability moderated the relationship between these specific skills and nonword repetition performance. Results showed all four predictor variables were related to nonword repetition performance, accounting for 59% of variance. The variable with the strongest association with nonword repetition was phonological memory, followed by oromotor sequencing ability, word reading, and oromotor control. Contrary to expectations, neither speech nor language ability were significantly associated with the degree to which these specific skills were drawn upon to perform the nonword repetition task. These findings underline the multidimensional nature of the nonword repetition task and provide further evidence of the major contributions made by phonological memory, word reading, speech sequencing and control to performance on this task. Further, findings suggest that speech and language ability, as measured here, do not significantly influence the skills employed for nonword repetition performance.

Pathogenic variants in DDX3X have recently been identified to be a relatively common cause of intellectual disability in females. In this study, we describe six female probands, from five unrelated families, with five novel heterozygous variants in DDX3X, and the identification of potential germline mosaicism. Consistent features between this cohort and previously described cases include developmental delay or intellectual disability, growth disturbance and movement disorder. Common facial dysmorphism within the cohort include short palpebral fissures, micrognathia, bulbous nasal tip, protruding ears, high arched palate, thin upper vermillion and smooth philtrum. Novel clinical features identified from this cohort include facial dysmorphisms, perinatal complications, valgus feet deformity, lipoatrophy, dystonic episodes, and cutaneous mastocytosis. This case series attempts to expand the phenotype of the DDX3X syndrome; however, it remains heterogeneous. Description of further cases is required to more accurately identify the significance of novel phenotypes within this cohort.

Background: Submucous cleft palate (SMCP) has a heterogeneous presentation and is often identified late or misdiagnosed. Diagnosis is prompted by speech, resonance or feeding symptoms associated with velopharyngeal insufficiency. However, the broader impacts of SMCP on communication have rarely been examined and therefore are poorly understood. Aim: To describe the communicative profile of individuals with non-syndromic SMCP by examining speech, language and pragmatics (social language). Methods & Procedures: Fifteen participants with SMCP aged 5;1–12;8, without a genetic diagnosis, participated in the study. Participants completed standardized assessments examining language, resonance, speech and non-verbal intellect. Parents also completed the Children's Communication Checklist (CCC-2), which provided a measure of overall communicative ability, including pragmatic skills. Formal language outcomes were compared with two cohorts: 36 individuals with overt non-syndromic clefts and 129 individuals with no history of clefting. Outcomes & Results: Speech intelligibility was reduced secondary to hypernasality, disordered articulation and/or impaired phonology (n = 7) in children with SMCP. Poorer overall language outcomes were observed for children with SMCP compared with both those with overt clefts and no history of clefting (p < 0.001). Language scores for children with SMCP ranged from impaired (n = 6) to above the standardized mean (n = 4). Receptive and expressive language performance were independently correlated with non-verbal IQ (p < 0.01). Those with severe language impairment (n = 4) also had borderline or impaired non-verbal IQ. Parents reported that speech and semantics were the most affected sub-domains of communication, while scores were the highest for the initiation domain. Speech and language skills were correlated strongly with pragmatics (r = 0.877, p < 0.01). Conclusions & Implications: Overall, performance was variable within the SMCP group across speech, language and pragmatic assessments. In addition to well-documented speech difficulties, children with SMCP may have language or pragmatic impairments, suggesting that further neurodevelopmental influences may be at play. As such, for individuals with SMCP, additional clinical screening of language and pragmatic abilities may be required to ensure accurate diagnosis and guide both cleft and non-cleft related therapy programmes.

Purpose: The purpose of this study was to expand the genetic architecture of neurodevelopmental disorders, and to characterize the clinical features of a novel cohort of affected individuals with variants in ZNF142, a C 2 H 2 domain-containing transcription factor. Methods: Four independent research centers used exome sequencing to elucidate the genetic basis of neurodevelopmental phenotypes in four unrelated families. Following bioinformatic filtering, query of control data sets, and secondary variant confirmation, we aggregated findings using an online data sharing platform. We performed in-depth clinical phenotyping in all affected individuals. Results: We identified seven affected females in four pedigrees with likely pathogenic variants in ZNF142 that segregate with recessive disease. Affected cases in three families harbor either nonsense or frameshifting likely pathogenic variants predicted to undergo nonsense mediated decay. One additional trio bears ultrarare missense variants in conserved regions of ZNF142 that are predicted to be damaging to protein function. We performed clinical comparisons across our cohort and noted consistent presence of intellectual disability and speech impairment, with variable manifestation of seizures, tremor, and dystonia. Conclusion: Our aggregate data support a role for ZNF142 in nervous system development and add to the emergent list of zinc finger proteins that contribute to neurocognitive disorders.

Background The association between left hemisphere stroke and acute speech and language impairment is well documented in adults. However, little is known about this association in childhood arterial ischemic stroke. Here we examined potential predictors of acute speech (dysarthria and apraxia) and language impairments after childhood arterial ischemic stroke, including site of lesion. Methods Children with radiologically confirmed acute arterial ischemic stroke, admitted to a tertiary pediatric hospital from 2004 to 2012, were identified from an institutional registry. We examined the prevalence of dysarthria, apraxia, and language impairment within two weeks of the stroke. Associations with age at stroke event, lesion side (left, right, or bilateral), and arterial territory affected (anterior, posterior, or both) were assessed using logistic regression. Results Sixty-two children with mean age eight years (range three to 17 years) were identified. Strokes were located in the left (32%), right (44%), or both hemispheres (24%). Dysarthria (74%) and language impairment (50%) were frequent. Verbal dyspraxia was less common (11%). There was little evidence that variables of interest, including site of lesion, were significantly associated with increased odds of dysarthria or language impairment (all P > 0.49). Conclusions Regardless of age, children are at high risk of communication disorders after stroke. Unlike adults, left hemisphere stroke was not associated with either speech or language impairment in our cohort, suggesting there may be bihemispheric contribution to language function. Future studies are needed to examine whether the predictors examined here determine long-term outcomes.

Reinforcement Sensitivity Theory has been used to investigate personality in the development and maintenance of disordered eating. However, the vast majority of research from this perspective has been limited by the use of measures developed to assess the original theory, rather than the significantly revised theory, potentially overlooking key personality differences in eating disorder subtypes. The current study aimed to overcome limitations when using measures based on the original theory by investigating differences and similarities in reinforcement sensitivity across eating disorder subtypes and healthy controls. The measure based on the revised theory assesses i) reward sensitivity [goal-drive persistence; reward interest, reward reactivity], ii) impulsivity, iii) behavioural inhibition, and iv) threat sensitivity. A total of 374 women from the community participated, including those with a past or present AN-R diagnosis (AN-R = 109); those with a past or present binge-type ED (Binge-type = 132); and healthy controls (HC = 133). Participants completed a questionnaire assessing personality, eating disorder symptoms, and past or present eating disorder diagnoses. Results showed that both the AN-R and Binge-type groups were higher in behavioural inhibition and threat sensitivity compared to the HC group. The Binge-type group showed higher impulsivity relative to the AN-R and HC group, and lower Goal-Drive Persistence relative to the HC group. The AN-R group showed lower Reward Interest and Reward Responsiveness relative to the HC group. This study supports and extends previous research with the findings of heightened threat and anxiety sensitivity in those with diagnosed eating disorders. Additionally, among those with a past or present eating disorder, the findings implicate impulsivity in differentiating bingeing versus restricting subtypes.

Objective: Subclinical phenotypes of nonsyndromic cleft lip with or without cleft palate (CL ± P) may be identified from clinically “unaffected” relatives and could be associated with specific cleft-related gene mutations. It has been hypothesized that velopharyngeal insufficiency (VPI) may be a subclinical phenotype of interest in this population, but this has not been explored quantitatively with appropriate control cohorts. The aim of this case–control study was to compare VPI in at-risk clinically unaffected relatives of individuals with nonsyndromic CL ± P with a low-risk matched normative Australian cohort. Participants: Clinically unaffected (ie, with no overt cleft) first-degree relatives of a proband with nonsyndromic CL ± P (n = 189) and noncleft controls (n = 207). Main Outcome Measure(s): Perceptual measures of VPI encompassing resonance, nasal emission, and articulation were evaluated using the Great Ormond Street Speech Assessment. Quantitative measures of VPI were obtained from the Nasometer II using standardized adult and pediatric speech stimuli. Results: Both perceptual and instrumental measures showed no significant difference ( P > .01) between the VPI in unaffected relatives and the noncleft comparison group. Mean nasalance scores for both groups were calculated and reported according to speech stimuli, age, and sex. Conclusions: Results suggest that VPI, measured through speech, is not a significant subclinical phenotype of nonsyndromic CL ± P. Therefore, further familial genetic investigations exploring VPI may not yield meaningful results. Exploration across multiple subclinical phenotypes in larger cohorts may enable researchers to better understand the multifaceted nature of this complex and heterogeneous anomaly.

PurposeUnderstanding what limits speech development in minimally verbal (MV) children with autism spectrum disorder (ASD) is important for providing highly effective targeted therapies. This preliminary investigation explores the extent to which developmental speech deficits predicted by Directions Into Velocities of Articulators (DIVA), a computational model of speech production, exemplify real phenotypes.MethodImplementing a motor speech disorder in DIVA predicted that speech would become highly variable within and between tokens, while implementing a motor speech plus an auditory processing disorder predicted that DIVA's speech would become highly centralized (schwa-like). Acoustic analyses of DIVA's output predicted that acoustically measured phoneme distortion would be similar between the two cases, but that in the former case, speech would show more within- and between-token variability than in the latter case. We tested these predictions quantitatively on the speech of children with MV ASD. In Study 1, we tested the qualitative predictions using perceptual analysis methods. Speech pathologists blinded to the purpose of the study tallied the signs of childhood apraxia of speech that appeared in the speech of 38 MV children with ASD. K-means clustering was used to create two clusters from the group of 38, and analysis of variance was used to determine whether the clusters differed according to perceptual features corresponding to within- and between-token variability. In Study 2, we employed acoustic analyses on the speech of the child from each cluster who produced the largest number of analyzable tokens to test the predictions of differences in within-token variability, between-token variability, and vowel space area.ResultsClusters produced by k-means analysis differed by perceptual features that corresponded to within-token variability. Nonsignificant differences between clusters were found for features corresponding to between-token variability. Subsequent acoustic analyses of the selected cases revealed that the speech of the child from the high-variability cluster showed significantly more quantitative within- and between-token variability than the speech of the child from the low-variability cluster. The vowel space of the child from the low-variability cluster was more centralized than that of typical children and that of the child from the high-variability cluster.ConclusionsResults provide preliminary evidence that subphenotypes of children with MV ASD may exist, characterized by (a) comorbid motor speech disorder and (b) comorbid motor speech plus auditory processing disorder. The results motivate testable predictions about how these comorbidities affect speech.Supplemental Materialhttps://doi.org/10.23641/asha.14384432

Contains fulltext : 237908.pdf (Publisher’s version ) (Closed access) Expressive communication impairment is associated with haploinsufficiency of SETBP1, as reported in small case series. Heterozygous pathogenic loss-of-function (LoF) variants in SETBP1 have also been identified in independent cohorts ascertained for childhood apraxia of speech (CAS), warranting further investigation of the roles of this gene in speech development. Thirty-one participants (12 males, aged 0; 8-23; 2 years, 28 with pathogenic SETBP1 LoF variants, 3 with 18q12.3 deletions) were assessed for speech, language and literacy abilities. Broader development was examined with standardised motor, social and daily life skills assessments. Gross and fine motor deficits (94%) and intellectual impairments (68%) were common. Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%) being the most common diagnosis. In contrast to past reports, the understanding of language was rarely better preserved than language expression (29%). Language was typically low, to moderately impaired, with commensurate expression and comprehension ability. Children were sociable with a strong desire to communicate. Minimally verbal children (32%) augmented speech with sign language, gestures or digital devices. Overall, relative to general development, spoken language and literacy were poorer than social, daily living, motor and adaptive behaviour skills. Our findings show that poor communication is a central feature of SETBP1 haploinsufficiency disorder, confirming this gene as a strong candidate for speech and language disorders.

AIM To delineate the speech and language phenotype of a cohort of individuals with FOXP1-related disorder. METHOD We administered a standardized test battery to examine speech and oral motor function, receptive and expressive language, non-verbal cognition, and adaptive behaviour. Clinical history and cognitive assessments were analysed together with speech and language findings. RESULTS Twenty-nine patients (17 females, 12 males; mean age 9y 6mo; median age 8y [range 2y 7mo-33y]; SD 6y 5mo) with pathogenic FOXP1 variants (14 truncating, three missense, three splice site, one in-frame deletion, eight cytogenic deletions; 28 out of 29 were de novo variants) were studied. All had atypical speech, with 21 being verbal and eight minimally verbal. All verbal patients had dysarthric and apraxic features, with phonological deficits in most (14 out of 16). Language scores were low overall. In the 21 individuals who carried truncating or splice site variants and small deletions, expressive abilities were relatively preserved compared with comprehension. INTERPRETATION FOXP1-related disorder is characterized by a complex speech and language phenotype with prominent dysarthria, broader motor planning and programming deficits, and linguistic-based phonological errors. Diagnosis of the speech phenotype associated with FOXP1-related dysfunction will inform early targeted therapy. What this paper adds Individuals with FOXP1-related disorder have a complex speech and language phenotype. Dysarthria, which impairs intelligibility, is the dominant feature of the speech profile. No participants were receiving speech therapy for dysarthria, but were good candidates for therapy Features of speech apraxia occur alongside persistent phonological errors. Language abilities are low overall; however, expressive language is a relative strength.

Purpose This systematic review critically appraises and maps the evidence for stuttering interventions in childhood and adolescence. We examine the effectiveness of speech-focused treatments, the efficacy of alternative treatment delivery methods and identify gaps in the research evidence. Methods Nine electronic databases and three clinical trial registries were searched for systematic reviews, randomised controlled trials (RCTs) and studies that applied an intervention with children (2–18 years) who stutter. Pharmacological interventions were excluded. Primary outcomes were a measure of stuttering severity and quality assessments were conducted on all included studies. Results Eight RCTs met inclusion criteria and were analysed. Intervention approaches included direct (i.e. Lidcombe Program; LP) and indirect treatments (e.g. Demands and Capacities Model; DCM). All studies had moderate risk of bias. Treatment delivery methods included individual face-to-face, telehealth and group-based therapy. Both LP and DCM approaches were effective in reducing stuttering in preschool aged children. LP had the highest level of evidence (pooled effect size=-3.8, CI -7.3 to -0.3 for LP). There was no high-level evidence for interventions with school-aged children or adolescents. Alternative methods of delivery were as effective as individual face-to-face intervention. Conclusion The findings of this systematic review and evidence mapping are useful for clinicians, researchers and service providers seeking to understand the existing research to support the advancement of interventions for children and adolescence who stutter. Findings could be used to inform further research and support clinical decision-making.

To explore the characteristics and associated factors of oromotor dysfunction in minimally verbal children with cerebral palsy (CP) aged five to six years, recruited from a population-based registry.Twenty children with CP who were minimally verbal completed a standardised, observational oromotor assessment. Linear regression analyses examined the relationship between oromotor dysfunction and potential associated factors (e.g., fine and gross motor function, communication, and feeding).Oromotor dysfunction affected every participant and was identified in all structures examined (i.e., face, jaw, lips, and tongue). Oromotor movements showed little dissociation among jaw, lip, and tongue movements. Oromotor dysfunction was univariately associated with the Manual Ability Classification System levels IV-V (Oromotor dysfunction was highly prevalent in our sample of minimally verbal children with CP, having significant functional impacts on feeding and communication. Findings suggest that fine motor function (i.e., Manual Ability Classification System levels IV-V) is a stronger predictor than gross motor function for identifying children with CP who are minimally verbal and at risk of oromotor dysfunction. IMPLICATIONS FOR REHABILITATIONOromotor dysfunction was highly prevalent in our sample of minimally verbal children with cerebral palsy.Severe fine motor impairment strongly predicted oromotor dysfunction, indicating that fine motor function may provide an early indicator of impaired oromotor function for this clinical population.Robust, standardised measures of motor speech-related oromotor development suitable for children with cerebral palsy who are minimally verbal are lacking.Until such a measure is developed, formal evaluation may be achieved via oral motor assessments standardised for typically developing children, with the caveat one must interpret the results with caution.

This article is protected by copyright. All rights reserved. BACKGROUND: There is a lack of population-based studies exploring the communicative behaviours of minimally verbal children with cerebral palsy (CP), with factors associated with superior and poorer communication outcomes unknown. This study aimed to examine the communication behaviours of minimally verbal children with CP recruited from a representative community sample, and to identify factors associated with communication outcomes. METHODS: Twenty minimally verbal children aged 5-6 years, recruited through the Victorian Cerebral Palsy Register, completed the Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP). Linear regressions examined child-related and environmental factors associated with communication outcomes. RESULTS: CSBS-DP total raw scores ranged from 0-113. Strengths were the use of conventional gestures and understanding of language. Challenges were noted in using sequential action schemes during play. Communication typically served to regulate the behaviour of others. All participants demonstrated reduced functional communication (Communication Function Classification System levels III-IV). In the multivariable regression model adjusted for cognition, poorer communication skills were associated with Manual Ability Classification System levels IV-V (p=0.004). CONCLUSIONS: Whilst some children with CP who are minimally verbal use a variety of communication functions, significant functional limitations may be apparent. Severe upper limb impairment may provide an early indication of greater communication difficulties.

Aim To examine the frequency, characteristics, and factors associated with speech delay and disorder in a community sample of children with cerebral palsy (CP). Method Participants were 84 children (37 females, 47 males; aged between 4y 11mo–6y 6mo) with CP identified through a population-based registry. Speech and oromotor function were systematically evaluated to provide a differential diagnosis of articulation, phonological, and motor speech disorders. Results In total, 82% (69/84) of participants had delayed or disordered speech production, including minimally verbal presentations (n=20). Verbal participants (n=64) presented with dysarthria (78%), articulation delay or disorder (54%), phonological delay or disorder (43%), features of childhood apraxia of speech (CAS) (17%), or mixed presentations across these conditions. Speech intelligibility was poorest in those with dysarthria and features of CAS. Speech delay or disorder in verbal participants was associated with language impairment (p=0.002) and reduced health-related quality of life (p=0.04) (Fisher’s exact test). Poorer speech accuracy (i.e. lower percentage consonants correct) correlated with greater impairments in both language (p

Communication difficulties are a core feature of Phelan-McDermid syndrome (PMS). However, a specific speech and language phenotype has not been delineated, preventing prognostic counselling and development of targeted therapies. We examined speech, language, social and functional communication abilities in 21 individuals with PMS (with SHANK3 involvement), using standardised assessments. Mean age was 9.7 years (SD 4.1) and 57% were female. Deletion size ranged from 41 kb to 8.3 Mb. Nine participants (45%) were non-verbal. Four (19%) had greater verbal ability, speaking in at least 4–5 word sentences, but with speech sound errors. Standard scores for receptive and expressive language were low (typically >3 SD below the mean). Language age equivalency was 13–16 months on average (range 2–53 months). There was a significant association between deletion size and the ability to use phrases. Participants with smaller deletion sizes were more likely to be able to use phrases (odds ratio: 0.36, 95% CI: 0.14–0.95, p = 0.040). Adaptive behaviour (life skills) was low in all areas (>2 SD below mean). Scores in communication were markedly lower than for daily living (p = 0.008) and socialisation (p

Feeding difficulties threaten growth, health and neurodevelopment, and are prevalent among infants born preterm. The literature differs on (i) whether these problems persist into early childhood, and (ii) risk factors in the preterm population. In this study we explore feeding difficulties and risk factors in preterm and term-born three-year-olds.To determine whether three-year-olds born30 weeks have poorer feeding outcomes than their term-born peers; and identify predictors of feeding outcomes in children born30 weeks.Feeding outcomes were examined in three-year-old children born30 weeks, and a term-born comparison group, using parent report and the Behavioral Pediatric Feeding Assessment Scale (BPFAS). Factors hypothesized to be associated with feeding difficulties and preterm birth were examined in the preterm group, including: gestational age at birth, birth weight z-score, chronic lung disease (CLD), nasogastric tube (NGT) feeding at hospital discharge, age at breastfeeding cessation, oromotor feeding impairment at 12 months, weight at 12 months in kilograms and neurodevelopmental diagnoses.In 217 children (111 born30 weeks, 106 term-born), parents of children born30 weeks reported more feeding concerns on parent report questions than parents of term-born peers. CLD, NGT at discharge, neurodevelopmental diagnoses and weight at 12 months predicted these parent-reported outcomes. By contrast, there was no difference in BPFAS results between preterm and term groups, and BPFAS scores were predicted only by birth-weight z-score in the preterm group.Behavioral feeding outcomes for three-year-old children born30 weeks were equivalent to term-born peers in this study, however parental concerns about feeding differed. Further investigation is required to identify the drivers of parent concerns about feeding. Children displaying core risk factors warrant specific follow-up of feeding outcomes.

Childhood apraxia of speech (CAS) is a rare disorder of childhood that can leave a watermark of the impacts throughout the lifetime. Since being first described in the 1950s, aetiological insights have been limited. At a neurobiological level, clinical MRI scans fail to reveal overt neural anomalies in individual cases with CAS, although quantitative MRI methods have revealed subtle brain anomalies at a group level. Dramatic insights, however, occurred in the past decade from the discovery of genetic pathways underlying the phenotype. Several single genes and copy number-variant conditions are now associated with CAS either in relative isolation, as in the case of FOXP2 variants, or most typically in association with other neurodevelopmental conditions, such as epilepsy, intellectual disability, motor impairment and autism. CAS requires careful differential diagnosis from other childhood speech disorders, but when a severe and persistent diagnosis is confirmed, a genetic aetiology should increasingly be pursued.