RESUMEN
Fourteen Speech and Language Therapists/Pathologists (SLT/Ps) from 13 countries across 5 continents made up the International Confederation of Cleft Lip and Palate and Related Craniofacial Anomalies (ICCPCA) CLEFT 2022 Speech Taskforce. Following a group consensus activity led by an external facilitator using Lightning Design Thinking principles, "task-shifting" was identified as the topic for this Taskforce. Absence and scarcity of SLT/Ps in many parts of the world have led to non-SLT/Ps delivering speech and language therapy services to individuals with cleft lip +/- palate. This narrative is the first known attempt to develop a framework, describing the different types of providers and their scope of practice.
RESUMEN
Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., "Critical-Exon Genes (CEGs)"] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package. Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients' pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients.
RESUMEN
This study explored the physical and clinical phenotype of Bangladeshi children with autism spectrum disorder (ASD). A totally of 283 children who were referred for screening and administered Module 1 of the Autism Diagnostic Observation Schedule (ADOS) were included. Overall, 209 met the ADOS algorithmic cutoff for ASD. A trend for greater weight and head circumference was observed in children with ASD versus non-ASD. Head circumference was significantly (p < 0.03) larger in ASD males compared with non-ASD males. A trend was also observed for symptom severity, higher in females than males (p = 0.068), with further analyses demonstrating that social reciprocity (p < 0.014) and functional play (p < 0.03) were significantly more impaired in ASD females than males. The findings help understand sex differences in ASD.
