Cristina Mei

A highly penetrant form of childhood apraxia of speech due to deletion of 16p11.2

Individuals with heterozygous 16p11.2 deletions reportedly suffer from a variety of difficulties with speech and language. Indeed, recent copy-number variant screens of children with childhood apraxia of speech (CAS), a specific and rare motor speech disorder, have identified three unrelated individuals with 16p11.2 deletions. However, the nature and prevalence of speech and language disorders in general, and CAS in particular, is unknown for individuals with 16p11.2 deletions. Here we took a genotype-first approach, conducting detailed and systematic characterization of speech abilities in a group of 11 unrelated children ascertained on the basis of 16p11.2 deletions. To obtain the most precise and replicable phenotyping, we included tasks that are highly diagnostic for CAS, and we tested children under the age of 18 years, an age group where CAS has been best characterized. Two individuals were largely nonverbal, preventing detailed speech analysis, whereas the remaining nine met the standard accepted diagnostic criteria for CAS. These results link 16p11.2 deletions to a highly penetrant form of CAS. Our findings underline the need for further precise characterization of speech and language profiles in larger groups of affected individuals, which will also enhance our understanding of how genetic pathways contribute to human communication disorders.

Activities and participation of children with cerebral palsy: parent perspectives

Abstract Purpose: To explore parents’ views of the activities and participation of children with cerebral palsy (CP) with a range of communicative abilities and the factors (personal and environmental) that influenced these. Methods: Thirteen parents of children with CP aged 4—9 years participated in semi—structured individual interviews. Interviews were recorded, transcribed and analysed thematically. Identified codes and themes were mapped to the domains of the International Classification of Functioning, Disability and Health — Children and Youth Version (ICF-CY). Results: Parents’ responses reflected all ICF-CY domains comprising activity, participation and environmental factors. Codes were primarily mapped to the domains learning and applying knowledge, communication, mobility and interpersonal interactions and relationships. Key barriers identified included aspects of parents’ own interactions with their child (e.g. not offering choices), unfamiliar people and settings, negative attitudes of others and children’s frustration. Facilitators included support received from the child’s family and school, being amongst children, having a familiar routine and the child’s positive disposition. Conclusions: Despite the barriers experienced, children participated in a range of activities. Parents placed importance on communication and its influence on children’s independence, behaviour and relationships. Barriers and facilitators identified highlight aspects of the environment that could be modified through intervention to enhance communication and participation. Implications for Rehabilitation Children’s activities and participation were largely related to early learning tasks (e.g. literacy), communication, mobility and interactions. Intervention aimed at improving activities and participation may address the various child, impairment, social and environment factors identified here as impacting on activities and participation (e.g. the child’s personal characteristics, communication and physical impairments, the support and attitudes of others and the familiarity of the environment). Therapists will need to consider (and manage) the potential negative impact communication deficits may have on children’s behaviour, independence and social skills which may in turn detrimentally impact on activity and participation.

Motor speech impairment, activity, and participation in children with cerebral palsy

Abstract The present study used a population-based sample of children with cerebral palsy (CP) to estimate the prevalence of motor speech impairment and its association with activity and participation. A sample of 79 Victorian children aged 4 years 11 months to 6 years 5 months was recruited through the Victorian CP Register. The presence of motor speech impairment was recorded using the Viking Speech Scale (VSS). Activity and participation outcomes included speech intelligibility (the National Technical Institute for the Deaf rating scale, NTID), the Functional Communication Classification System (FCCS) and Communication Function Classification System (CFCS). A parent completed rating scale was used to examine the association between motor speech impairment and participation. Ninety per cent (71/79) of children demonstrated a motor speech impairment. Strong associations were found between the VSS and NTID (< .001), CFCS (< .001), and FCCS levels (<.001). VSS levels III–IV were significantly associated with restrictions in home, school, and community-based participation as perceived by parents. Although some diversity in activity and participation outcomes was observed within specific VSS levels, the results of this study suggested that children with mild motor speech impairments are more likely to demonstrate superior activity and participation outcomes compared to children with moderate or severe deficits.

Speech and language in a genotyped cohort of individuals with Kabuki syndrome

Speech and language deficits are commonly associated with Kabuki syndrome. Yet little is known regarding the specific symptomatology of these disorders, preventing use of targeted treatment programs. Here we detail speech and language in 16 individuals with Kabuki syndrome (thirteen with KMT2D mutations, one with a KDM6A mutation, and two mutation‐negative cases), aged 4–21 years. The most striking speech deficit was dysarthria, characterised by imprecise consonants, harsh vocal quality, hypernasality, reduced rate and stress, and distorted pitch. Oromotor functioning was also impaired. Delayed, rather than disordered, articulation and phonology was common. Both receptive and expressive language abilities were reduced in the majority and deficits were noted across all language sub‐domains (i.e., semantics, syntax, morphology, and pragmatics) with no clear differentiation or specific language profile. Individuals with Kabuki syndrome present with a heterogenous pattern of oromotor, speech, and language deficits. This variability fits with the multisystem nature of the disorder, which may encompass neurological, orofacial structural, hearing, and cognitive deficits, any or all of which may contribute to speech or language impairment. Our results suggest that all individuals with Kabuki syndrome have some level of communication deficit, warranting speech pathology involvement in all cases.

Language Outcomes of Children with Cerebral Palsy aged 5 years and 6 years: A Population-Based Study

To examine the frequency, range, and features of language impairment in a community sample of children with cerebral palsy (CP) aged 5 to 6 years.

Who to Refer for Speech Therapy at 4 Years of Age Versus Who to “Watch and Wait”?

Objective To examine predictors of speech disorder resolution versus persistence at age 7 years in children with speech errors at age 4 years. Study design Participants were drawn from a longitudinal, community cohort. Assessment at age 4 years (N = 1494) identified children with speech errors. Reassessment at age 7 years allowed categorization into resolved or persistent categories. Logistic regression examined predictors of speech outcome, including family history, sex, socioeconomic status, nonverbal intelligence, and speech error type (delay vs disorder). Results At age 7 years, persistent errors were seen in over 40% of children who had errors at age 4 years. Speech symptomatology was the only significant predictor of outcome (P = .02). Children with disordered errors at age 4 years were twice as likely to have poor speech outcomes at age 7 years compared with those with delayed errors. Conclusions Children with speech delay at age 4 years seem more likely to resolve, and this might justify a “watch and wait” approach. In contrast, those with speech disorder at age 4 years appear to be at greater risk for persistent difficulties, and could be prioritized for therapy to offset long‐term impacts.

Benchmarking clinical practice against best evidence: An example from breastfeeding infants with cleft lip and/or palate

The purpose of this paper was to systematically review the literature to determine the feasibility of breastfeeding children with cleft lip and/or palate (CL+/−P) and determine whether Australian cleft-unit guidelines reflect best practice. The methodology used was a systematic review of the literature regarding breastfeeding for infants with CL+/−P. Guidelines regarding the breastfeeding of infants with CL+/−P from Australian cleft units were also reviewed. We then compared these guidelines against evidence from the systematic review to determine whether Australian cleft units were basing clinical management on current best evidence. Results suggested that infants with a cleft lip may breastfeed with few difficulties, whilst infants with a cleft palate or cleft lip and palate typically present with greater feeding difficulties and thus require bottle-feeding in conjunction with breastfeeding to meet their nutritional needs. However, much of the evidence was considered weak. Breastfeeding guidelines were provided by 7/9 cleft units. Of the 17 different recommendations made across the guidelines, 76% (13/17) were supported by evidence. The main conclusion drawn was that current best evidence supports breastfeeding for all children with CL+/−P, but children with cleft palate and cleft lip and palate will typically require additional nutritional supplementation with bottle-feeding. There was fair adherence to evidence-based practice in Australia, with the majority of guidelines being underpinned by evidence. Speech–language pathologists working with different populations who are interested in benchmarking their institutions clinical care against current best evidence and nationwide practice could use methodology similar to that applied in the present study.

Deep phenotyping of speech and language skills in individuals with 16p11.2 deletion

Recurrent deletions of a ~600-kb region of 16p11.2 have been associated with a highly penetrant form of childhood apraxia of speech (CAS). Yet prior findings have been based on a small, potentially biased sample using retrospectively collected data. We examine the prevalence of CAS in a larger cohort of individuals with 16p11.2 deletion using a prospectively designed assessment battery. The broader speech and language phenotype associated with carrying this deletion was also examined. 55 participants with 16p11.2 deletion (47 children, 8 adults) underwent deep phenotyping to test for the presence of CAS and other speech and language diagnoses. Standardized tests of oral motor functioning, speech production, language, and non-verbal IQ were conducted. The majority of children (77%) and half of adults (50%) met criteria for CAS. Other speech outcomes were observed including articulation or phonological errors (i.e., phonetic and cognitive-linguistic errors, respectively), dysarthria (i.e., neuromuscular speech disorder), minimal verbal output, and even typical speech in some. Receptive and expressive language impairment was present in 73% and 70% of children, respectively. Co-occurring neurodevelopmental conditions (e.g., autism) and non-verbal IQ did not correlate with the presence of CAS. Findings indicate that CAS is highly prevalent in children with 16p11.2 deletion with symptoms persisting into adulthood for many. Yet CAS occurs in the context of a broader speech and language profile and other neurobehavioral deficits. Further research will elucidate specific genetic and neural pathways leading to speech and language deficits in individuals with 16p11.2 deletions, resulting in more targeted speech therapies addressing etiological pathways.

Early speech development in Koolen de Vries syndrome limited by oral praxis and hypotonia

Communication disorder is common in Koolen de Vries syndrome (KdVS), yet its specific symptomatology has not been examined, limiting prognostic counselling and application of targeted therapies. Here we examine the communication phenotype associated with KdVS. Twenty-nine participants (12 males, 4 with KANSL1 variants, 25 with 17q21.31 microdeletion), aged 1.0–27.0 years were assessed for oral-motor, speech, language, literacy, and social functioning. Early history included hypotonia and feeding difficulties. Speech and language development was delayed and atypical from onset of first words (2; 5–3; 5 years of age on average). Speech was characterised by apraxia (100%) and dysarthria (93%), with stuttering in some (17%). Speech therapy and multi-modal communication (e.g., sign-language) was critical in preschool. Receptive and expressive language abilities were typically commensurate (79%), both being severely affected relative to peers. Children were sociable with a desire to communicate, although some (36%) had pragmatic impairments in domains, where higher-level language was required. A common phenotype was identified, including an overriding ‘double hit’ of oral hypotonia and apraxia in infancy and preschool, associated with severely delayed speech development. Remarkably however, speech prognosis was positive; apraxia resolved, and although dysarthria persisted, children were intelligible by mid-to-late childhood. In contrast, language and literacy deficits persisted, and pragmatic deficits were apparent. Children with KdVS require early, intensive, speech motor and language therapy, with targeted literacy and social language interventions as developmentally appropriate. Greater understanding of the linguistic phenotype may help unravel the relevance of KANSL1 to child speech and language development.

Ultra-high-risk paradigm: lessons learnt and new directions

Within the embryonic early psychosis field in the early 1990s, the conceptualisation and definition of an at-risk or ultra-high-risk (UHR) mental state for psychosis was a breakthrough which transformed the clinical and research landscape in psychiatry. Twenty-five years later, we have a new evidence base that has illuminated the neurobiology of the onset phase of psychotic disorder, delivered Cochrane level 1 evidence showing that the onset of full-threshold sustained psychotic disorder can be at least delayed, and is paving the way to a new generation of transdiagnostic research. Here, we document the contribution of the UHR approach to understanding the underlying mechanisms of psychosis onset as well as the long-term outcomes. Particularly, we highlight that psychosis onset can be delayed in those meeting UHR criteria and that these criteria have a higher valence for subsequent psychotic disorders and some valence for persistent non-psychotic syndromes. Critiques have helped to identify some of the limitations of this paradigm, which are acknowledged. These include evidence that psychotic disorders can emerge more acutely and from other, as yet undefined, precursor states. Rather than defending, or alternatively questioning the value of, the UHR approach, we propose a broader, transdiagnostic staging model that is consistent with the pluripotent and variably comorbid trajectories for mental disorders. This approach moves beyond psychosis to capture a wider range of subthreshold symptoms and full-threshold disorders, thus enhancing prediction for the emergence and progression of a range of mental disorders, as well as providing new avenues for early intervention and prevention.