This study focuses on the comorbidity between attention-deficit/hyperactivity disorder (ADHD) symptoms and speech sound disorder (SSD). SSD is a developmental disorder characterized by speech ...production errors that impact intelligibility. Previous research addressing this comorbidity has typically used heterogeneous groups of speech–language disordered children. This study employed more precise speech–language diagnostic criteria and examined ADHD symptomatology in 108 SSD children between the ages of 4 and 7 years old with specific language impairment (SLI) (
n
= 23, 14 males, 9 females) and without SLI (
n
= 85, 49 males, 36 females). We also examined whether a subcategory of SSD, persistent (
n
= 39, 25 males, 14 females) versus normalized SSD (
n
= 67, 38 males, 29 females), was associated with ADHD and/or interacted with SLI to predict ADHD symptomatology. Results indicated that participants in the SSD + SLI group had higher rates of inattentive ADHD symptoms than those in the SSD-only and control groups. In addition, an unexpected interaction emerged such that children with SLI and normalized-SSD had significantly higher ADHD inattentive ratings than the other subgroups. A proposed explanation for this interaction is discussed.
It has long been recognized that from the first months of life auditory perception plays a crucial role in speech and language development. Only in recent years, however, is the precise mechanism of ...auditory development and its interaction with the acquisition of speech and language beginning to be systematically revealed. This paper presents the results of a series of studies exploring the relevance of electrophysiological measurements for the objective diagnosis of children with language and speech disorders. In the first, retrospective, study, an inventory was made of clinical neurological, neuropsychological, logopedic and neurophysiological findings obtained from 43 children referred to the Paediatric Neurology Centre for the diagnosis of their speech and language deficits. Neurophysiological abnormalities were found in 95% of these children, among these deviant auditory evoked potentials (AEVPs). The second study demonstrated developmental trends in the waveform of the cortical AEVPs up to age 6 years; the implications for longitudinal studies are discussed. Preliminary results from the third study show emerging differences in auditory event-related potentials (AERPs) for young children who are at risk for developmental dyslexia based on their family history. These findings underscore the clinical usefulness of neurophysiological measures for the diagnosis of speech-language disorders. Clinical protocols are further developed and tested.
The speech and language functioning of a group of 20 children (aged 8-16) who had sustained a closed head injury at least 12 months previously were assessed with the purpose of developing a ...comprehensive profile of the type and severity of the long-term speech/language disorders exhibited by this group. The subjects were administered a battery of speech/language assessments including an articulation/phonological assessment; oromotor assessment; overall language test and specific language skills assessments. Performance of the head-injured group was compared to that of a group of non-neurologically impaired accident victims matched for age, sex and socioeconomic status. Overall language performance scores of the head-injured group were found to be significantly lower than achieved by the control group.
POU3F3, also referred to as Brain-1, is a well-known transcription factor involved in the development of the central nervous system, but it has not previously been associated with a ...neurodevelopmental disorder. Here, we report the identification of 19 individuals with heterozygous POU3F3 disruptions, most of which are de novo variants. All individuals had developmental delays and/or intellectual disability and impairments in speech and language skills. Thirteen individuals had characteristic low-set, prominent, and/or cupped ears. Brain abnormalities were observed in seven of eleven MRI reports. POU3F3 is an intronless gene, insensitive to nonsense-mediated decay, and 13 individuals carried protein-truncating variants. All truncating variants that we tested in cellular models led to aberrant subcellular localization of the encoded protein. Luciferase assays demonstrated negative effects of these alleles on transcriptional activation of a reporter with a FOXP2-derived binding motif. In addition to the loss-of-function variants, five individuals had missense variants that clustered at specific positions within the functional domains, and one small in-frame deletion was identified. Two missense variants showed reduced transactivation capacity in our assays, whereas one variant displayed gain-of-function effects, suggesting a distinct pathophysiological mechanism. In bioluminescence resonance energy transfer (BRET) interaction assays, all the truncated POU3F3 versions that we tested had significantly impaired dimerization capacities, whereas all missense variants showed unaffected dimerization with wild-type POU3F3. Taken together, our identification and functional cell-based analyses of pathogenic variants in POU3F3, coupled with a clinical characterization, implicate disruptions of this gene in a characteristic neurodevelopmental disorder.
Heterozygous pathogenic variants in various FOXP genes cause specific developmental disorders. The phenotype associated with heterozygous variants in FOXP4 has not been previously described.
We ...assembled a cohort of eight individuals with heterozygous and mostly de novo variants in FOXP4: seven individuals with six different missense variants and one individual with a frameshift variant. We collected clinical data to delineate the phenotypic spectrum, and used in silico analyses and functional cell-based assays to assess pathogenicity of the variants.
We collected clinical data for six individuals: five individuals with a missense variant in the forkhead box DNA-binding domain of FOXP4, and one individual with a truncating variant. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia, cervical spine abnormalities, and ptosis. Luciferase assays showed loss-of-function effects for all these variants, and aberrant subcellular localization patterns were seen in a subset. The remaining two missense variants were located outside the functional domains of FOXP4, and showed transcriptional repressor capacities and localization patterns similar to the wild-type protein.
Collectively, our findings show that heterozygous loss-of-function variants in FOXP4 are associated with an autosomal dominant neurodevelopmental disorder with speech/language delays, growth defects, and variable congenital abnormalities.
Children in the foster care system often face many educational challenges, including having an increased risk of language delays compared to the general population, with an estimated 35%–73% of the ...foster youth population experiencing language difficulties. Language delays are caused by many factors, but for children in foster care, one major antecedent is child abuse and neglect. Early delays greatly impact long‐term outcomes for children, including delays in their reading, writing, and social competence. This article explores possible causes of language delays for youths in foster care, describes the negative impact of language delays, and identifies evidence‐based practices for early intervention within the child welfare system and primary and secondary schools, specifically targeting practices for school psychologists, school counselors, school social workers, and speech pathologists.
Since its initial identification, the Forkhead Box P2 gene (
FOXP2
) has maintained its singular status as the archetypal monogenic determinant implicated in Mendelian forms of human speech and ...language impairments. Despite the passage of two decades subsequent to its discovery, extant literature remains disproportionately sparse with regard to case-specific instances and loci of mutational perturbations. The objective of the current investigation centers on furnishing an enriched delineation of both its clinical manifestations and its mutational heterogeneity. Clinical phenotypes and peripheral blood samples were assiduously amassed from familial subjects. Whole-exome sequencing and Sanger sequencing methodologies were deployed for the unambiguous identification of potential genetic variants and for corroborating their co-segregation within the family pedigree. An exhaustive review of published literature focusing on patients manifesting speech and language disorders consequent to
FOXP2
genetic anomalies was also undertaken. The investigation yielded the identification of a novel heterozygous variant, c.661del (p.L221Ffs*41), localized within the
FOXP2
gene in the proband, an inheritance from his symptomatic mother. The proband presented with an array of symptoms, encompassing dysarthric speech, deficits in instruction comprehension, and communicative impediments. In comparison, the mother exhibited attenuated symptoms, including rudimentary verbalization capabilities punctuated by pronounced stuttering and dysarthria. A comprehensive analysis of articles archived in the Human Gene Mutation Database (HGMD) classified under “DM” disclosed the existence of 74 patients inclusive of the subjects under current examination, sub-divided into 19 patients with null variants, 5 patients with missense variants, and 50 patients with gross deletions or complex genomic rearrangements. A conspicuous predominance of delayed speech, impoverished current verbal abilities, verbal comprehension deficits, and learning difficulties were observed in patients harboring null or missense
FOXP2
variants, as compared to their counterparts with gross deletions or complex rearrangements. Developmental delays, hypotonia, and craniofacial aberrations were exclusive to the latter cohort. The elucidated findings augment the existing corpus of knowledge on the genetic architecture influencing both the proband and his mother within this specified familial context. Of critical importance, these discoveries furnish a robust molecular framework conducive to the prenatal diagnostic evaluations of prospective progeny within this familial lineage.
Highlights ► Definitions and means of measuring temperament are provided. ► Five salient perspectives on temperament are described. ► Major theories of temperament discussed. ► Temperament re ...language disorders, stuttering and voice is discussed. ► Four possible relations between temperament and speech-language described.
•We prepared Tg mice expressing FOXP2 in the cerebellum by using Pcp2 promoter.•FOXP2 expression in the cerebellum partially improved USV in Foxp2(R552H)-KI mice.•Foxp2 in the cerebellum pertains to ...USVs modification but not their production.
The R553H mutation has been found in the FOXP2 gene of patients with speech-language disorder. Foxp2(R552H) knock-in (KI) mice exhibit poor dendritic development of Purkinje cells in the cerebellum and impaired ultrasonic vocalization (USV), which is related to human speech and language; compared with wild-type mice, heterozygous Foxp2(R552H)-KI pups exhibit the reduced number of whistle-type USVs and the increased short-type ones, while homozygous pups exhibit only click-type USVs but no whistle-type or short-type ones. To make clear the relationship between the role of Foxp2 in the cerebellum and whistle-type USVs activity, we prepared transgenic (Tg) mice specifically expressing human FOXP2-myc in cerebellum (Pcp2-FOXP2-myc-Tg mice) by using purkinje cell protein-2 (Pcp2) promoter. FOXP2-myc expression in the cerebellum increased the relative numbers of whistle-type USVs in the heterozygous Foxp2(R552H)-KI pups and recovered their USVs but did not in the homozygous ones. Foxp2 in the cerebellum may pertain to the brain network engaged in whistle-type USVs activities including modification, but not their production. There may be common molecular contribution of Purkinje cells to human FOXP2-mediated speech-language and mouse Foxp2-mediated USVs.
The purpose of this study is the development of language-intervention content,“Special Friend, iRobiQ.”The play-robot content serves various roles: The promotion of language interaction for children ...with speech-language disorders; an interlocutor friend (Talking Friend, iRobiQ); the transmission of data for diagnosis and evaluation between parents and experts; and a monitor for the supervisor of the speech-language disorder children outside of a therapy setting (Helping Friend, iRobiQ). This content design used a script approach, which provides entertaining educational elements for speech-language disorder children, as a player and learner. It has greetings and a birthday celebration script (cake, gift, song), with the theme of the practical language goals necessary for speech-language disorder children. The format provides a platform for the exchange of emotions as a peer. When examining the effectiveness of its adaptability for use in the field, four certified speech-language therapists used the content with four autism/MR (Mental Retardation) children who were 4–5 years old over eight sessions in October 2012. The children learned to initiate conversations with the robot with the emotional exchange of expressions, as reported positively. These results suggest the future development of speech-language therapist assistant robots.
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