Neurodevelopmental disorders are genetically and phenotypically heterogeneous encompassing developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), structural brain abnormalities, and neurological manifestations with variants in a large number of genes (hundreds) associated. To date, a few de novo mutations potentially disrupting TCF20 function in patients with ID, ASD, and hypotonia have been reported. TCF20 encodes a transcriptional co-regulator structurally related to RAI1, the dosage-sensitive gene responsible for Smith–Magenis syndrome (deletion/haploinsufficiency) and Potocki–Lupski syndrome (duplication/triplosensitivity). Genome-wide analyses by exome sequencing (ES) and chromosomal microarray analysis (CMA) identified individuals with heterozygous, likely damaging, loss-of-function alleles in TCF20. We implemented further molecular and clinical analyses to determine the inheritance of the pathogenic variant alleles and studied the spectrum of phenotypes. We report 25 unique inactivating single nucleotide variants/indels (1 missense, 1 canonical splice-site variant, 18 frameshift, and 5 nonsense) and 4 deletions of TCF20. The pathogenic variants were detected in 32 patients and 4 affected parents from 31 unrelated families. Among cases with available parental samples, the variants were de novo in 20 instances and inherited from 4 symptomatic parents in 5, including in one set of monozygotic twins. Two pathogenic loss-of-function variants were recurrent in unrelated families. Patients presented with a phenotype characterized by developmental delay, intellectual disability, hypotonia, variable dysmorphic features, movement disorders, and sleep disturbances. TCF20 pathogenic variants are associated with a novel syndrome manifesting clinical characteristics similar to those observed in Smith–Magenis syndrome. Together with previously described cases, the clinical entity of TCF20-associated neurodevelopmental disorders (TAND) emerges from a genotype-driven perspective.
A bstract — Statistical analysis of data from a field survey of 132 handicapped children confirmed that a questionnaire approach is reliable in identifying children with potential behavioural and co‐ordination problems within a dental environment. Assessment of the behaviour and co‐ordination of 2,082 handicapped children aged 3–16 years, inclusive, suggested that approximately 53 per cent were manageable in a normal dental surgery and 79 per cent had the necessary co‐ordination for routine dental care.
A game mod describes a modification within an existing commercial computer-based game that has been created by a user. By game modding, a user can participate in the creative process by taking the setting of their favorite game and customizing it for entertainment purposes or to convey information. For years, commercial computer-based game developers committed considerable resources towards preventing users from “hacking” into or “hijacking” their games. Now several computer-based game developers provide editors with their products to encourage users to create content, and to allow educators, for instance, to take advantage of the benefits and production quality of commercial computer games to create customized instruction. This paper focuses on mainstream, accessible games with straightforward modding tools that can be easily integrated into a learning environment.Request access from your librarian to read this chapter's full text.
A survey of 2,212 handicapped children was conducted in South Australia to provide basic information so that a dental service could be planned. The prevalence of various specified conditions is presented for both single and combined disabilities. The distribution of the various conditions between the sexes has been analysed.
