Expanding the molecular landscape of childhood apraxia of speech: evidence from a single-center experience.

Background: Childhood apraxia of speech (CAS) is a genetically heterogeneous pediatric motor speech disorder. The advent of whole exome sequencing (WES) and whole genome sequencing techniques has led to increased identification of pathogenic variants in CAS genes. In an as yet uncharacterized Italian cohort, we aimed both to identify new pathogenic gene variants associated with CAS, and to confirm the disease-related role of genes already reported by others. We also set out to refine the clinical and neurodevelopmental characterization of affected children, with the aim of identifying specific, gene-related phenotypes. Methods: In a single-center study aiming to explore the genetic etiology of CAS in a cohort of 69 Italian children, WES was performed in the families of the 34 children found to have no copy number variants. Each of these families had only one child affected by CAS. Results: High-confidence (HC) gene variants were identified in 7/34 probands, in two of whom they affected KAT6A and CREBBP, thus confirming the involvement of these genes in speech impairment. The other probands carried variants in low-confidence (LC) genes, and 20 of these variants occurred in genes not previously reported as associated with CAS. UBA6, ZFHX4, and KAT6A genes were found to be more enriched in the CAS cohort compared to control individuals. Our results also showed that most HC genes are involved in epigenetic mechanisms and are expressed in brain regions linked to language acquisition processes. Conclusion: Our findings confirm a relatively high diagnostic yield in Italian patients.

TABLET TOSCANA to Develop Innovative Organizational Models for Tele-Rehabilitation in Subjects with Congenital and Acquired Developmental Disabilities: A Wait-List Control Group Trial Protocol.

Background/Objectives: In recent years, the advent of new technologies has fostered their application in neuro-psychomotor and language rehabilitation, particularly since the COVID-19 pandemic. Tele-rehabilitation has emerged as an innovative and timely solution, enabling personalized interventions monitored by clinicians. TABLET TOSCANA project aims to develop innovative tele-rehabilitation organizational models in children, adolescents and young adults with congenital and acquired developmental disabilities, using the Virtual Reality Rehabilitation System (VRRS) Home Kit and the MedicoAmico APP. Methods: The trial is designed according to the CONSORT statement guidelines. The project encompasses three phases: adapting the technologies for pediatric use, validating them through a wait-list study, and analyzing feasibility and effectiveness data to define new organizational models. A randomized wait-list-control study with 100 subjects aged 6 to 30 years will compare tele-rehabilitation versus prosecution of standard care. Discussion: Although literature highlights tele-rehabilitation benefits such as improved access, cost savings, and enhanced treatment adherence, practical implementation remains limited (i.e., the definition of standardized procedures). TABLET TOSCANA project seeks to address these gaps by focusing on multi-domain treatments for neurodevelopmental disabilities and emphasizing the integration of tele-rehabilitation into local health services. Conclusion: The project aims to improve the continuity and intensity of care through innovative models that integrate tele-rehabilitation into local health services. The results could inform healthcare policies and promote the development of innovative and collaborative models of care, paving the way for more effective and widespread tele-rehabilitation solutions and fostering collaborative networks among professionals.

Far Transfer Effects of Trainings on Executive Functions in Neurodevelopmental Disorders: A Systematic Review and Metanalysis.

Executive Functions are a set of interrelated, top-down processes essential for adaptive goal-directed behaviour, frequently impaired across different neurodevelopmental disorders with variable degrees of severity. Many executive-function-training studies in children with neurodevelopmental disorders have focused on near effects, investigating post-treatment improvements on directly trained processes, while enhancements of skills not directly trained, defined as far effects, are less considered, albeit these could be extremely relevant for reducing the negative impact of a disorder's core symptomatology. This systematic review and metanalysis aims to investigate the far effect outcomes after EF training in children with different types of neurodevelopmental disorders. 17 studies met the inclusion criteria for the systematic review, while 15 studies were selected in the metanalysis. An overall statistically significant effect size was found in the majority of far effect outcome measures considered in the studies. In particular, trainings on executive functions determine significant far effects on daily life functioning (0.46, 95% CI: [0.05-0.87]) and clinical symptoms (0.33, 95% CI: [0.15-0.51]). Despite a high variability of the results, intensity, frequency and the laboratory/life contexts dimension seem to be the most influential variables in determining far effects. This systematic review and metanalysis highlights the need to measure far effects of executive function training in neurodevelopmental disorders, selecting treatments not only on directly targeted processes, but also according to far impacts on the functional weakness of the disorder.

Executive functions in children with specific learning disorders: Shedding light on a complex profile through teleassessment.

Executive Functions (EFs) are high-order cognitive processes relevant to learning and adaptation and frequently impaired in children with specific learning disorders (SLDs). This study aimed to investigate EFs in children with SLD and explore the role of specific EF-related subprocesses, such as stimuli processing and processing speed. Fifty-seven SLD and 114 typically developing (TD) children, matched for gender and age, completed four tasks measuring response inhibition, interference control, shifting, and updating on a web-based teleassessment platform. The results show that SLD children performed lower in all EF tasks than TD children, regardless of stimulus type and condition. Mediation analyses suggested that differences between the SLD and TD groups are mediated by EF-related subprocesses, offering an interpretative model of EF deficits in children with SLD.

Implicit learning in children with Childhood Apraxia of Speech.

BACKGROUND: Childhood Apraxia of Speech is a severe and persistent clinical subtype of Speech Sound Disorder. Given the difficulties in the acquisition, programming and control of the movements underlying speech and the slowdown in a wide range of non-linguistic skills, the difficulty in implicit learning of sequential information could play a role in the disorder, contributing to understand its etiopathological mechanisms and behavioral manifestations. AIMS: The present study was aimed at investigating implicit learning in children with Childhood Apraxia of Speech. METHODS AND PROCEDURES: Twenty-five children with Childhood Apraxia of Speech, aged between 4 and 12 years, were matched for IQ and age to a control group of 25 typically developing children. Implicit learning of participants was assessed by Serial Reaction Time Task. OUTCOME AND RESULTS: Children with Childhood Apraxia of Speech did not show implicit learning, as documented by the absence of differences between reaction times in the sequenced block and the random block, usually considered as a measure of implicit learning effect. CONCLUSION AND IMPLICATIONS: Our results underline an implicit learning deficit in children with Childhood Apraxia of Speech, supporting the concept of a disorder not only confined to the speech domain, but also involving non-linguistic skills, in a composite and complex picture.

Relationship among Connectivity of the Frontal Aslant Tract, Executive Functions, and Speech and Language Impairment in Children with Childhood Apraxia of Speech.

Childhood apraxia of speech (CAS) is a subtype of motor speech disorder usually co-occurring with language impairment. A supramodal processing difficulty, involving executive functions (EFs), might contribute to the cognitive endophenotypes and behavioral manifestations. The present study aimed to profile the EFs in CAS, investigating the relationship between EFs, speech and language severity, and the connectivity of the frontal aslant tract (FAT), a white matter tract involved in both speech and EFs. A total of 30 preschool children with CAS underwent speech, language, and EF assessments and brain MRIs. Their FAT connectivity metrics were compared to those of 30 children without other neurodevelopmental disorders (NoNDs), who also underwent brain MRIs. Alterations in some basic EF components were found. Inhibition and working memory correlated with speech and language severity. Compared to NoND children, a weak, significant reduction in fractional anisotropy (FA) in the left presupplementary motor area (preSMA) FAT component was found. Only speech severity correlated and predicted FA values along with the FAT in both of its components, and visual-spatial working memory moderated the relationship between speech severity and FA in the left SMA. Our study supports the conceptualization of a composite and complex picture of CAS, not limited to the speech core deficit, but also involving high-order cognitive skills.

Dialogic Reading to Empower Executive Functions in Preschoolers.

Among the interventions recently developed to enhance Executive Functions (EFs) in preschoolers, Quincey Quokka's Quest (QQQ) is an illustrated book proposing EF activities embedded within a shared reading framework (Howard et al., 2017). In the present study, the Italian version of QQQ (QQQIT) was tested in 20 typical developing 4-5 year old children. Standardized tests were used to assess EFs pre- and post- intervention. QQQIT was conducted once a week for 8 weeks in small groups. A positive trend was registered in QQQIT performances from the first to the last sessions and a significant improvement, in comparison to the control condition, was obtained in the Color and Form Game test. These results, supporting the feasibility of the QQQIT intervention and its efficacy in increasing shifting abilities, confirm the usefulness of ecological interventions to empower specific EF components in preschool contexts.