Faculty Bibliography

BACKGROUND:ASH1L-related intellectual developmental disorder represents an emerging neurodevelopmental syndrome with significant phenotypic heterogeneity (Cordova et al. in Genes (Basel). 15(4):423, 2024). Comprehensive genomic analysis demonstrates superior diagnostic yield compared with targeted approaches in complex neurodevelopmental presentations (Srivastava et al. in Genet Med. 21(11):2413-2421, 2019). CASE PRESENTATION/METHODS:This report describes a 6-year-old Central Asian (Uzbek) male patient with a history of global developmental delay who was diagnosed with mild autism spectrum disorder, attention-deficit/hyperactivity disorder, and a developmental expressive language disorder. Neuropsychological assessment revealed an uneven cognitive profile with average verbal abilities but below-average nonverbal reasoning. After uninformative targeted genetic panels, trio whole-genome sequencing identified a novel de novo heterozygous missense variant in ASH1L c.4043A > G (p.Lys1348Arg). This variant, absent in population databases, was classified as a variant of uncertain significance. However, in silico analysis predicted this variant to be probably damaging, and therefore, it emerged as the strongest candidate to explain the patient's phenotype. CONCLUSION/CONCLUSIONS:This case expands the known phenotypic spectrum of ASH1L-related disorders, demonstrating that a de novo missense variant can be associated with a milder neurodevelopmental phenotype, including borderline-to-average intellectual ability. These findings challenge suggestions that missense variants uniformly lead to more severe outcomes and underscores the importance of comprehensive genomic and deep clinical characterization to refine our understanding of gene-disease relationships.

OBJECTIVES/OBJECTIVE:This study examines the amount of recess that children 8 to 9 years of age receive in the United States and compares the group classroom behavior of children receiving daily recess with that of children not receiving daily recess. METHODS:This is a secondary analysis of a public-use data set, the Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999, third-grade data set. Children were categorized into 2 levels of recess exposure, that is, none/minimal break (<1 break of 15 minutes/day) or some recess. Some recess was further categorized into 5 levels on the basis of frequency and duration of recess. Child, parent, school, and classroom characteristics of those with and without recess were compared. The group classroom behavior was assessed by using the teacher's rating of class behavior. RESULTS:Complete data were available for 10301 to 11624 children 8 to 9 years of age. There were equal numbers of boys and girls (boys: 50.3%). Children exposed to none/minimal break (30%) were much more likely to be black, to be from families with lower incomes and lower levels of education, to live in large cities, to be from the Northeast or South, and to attend public school, compared with those with recess. Teacher's rating of classroom behavior scores were better for children with some recess than for those with none/minimal break. This finding was maintained in multivariate regression analysis. However, among children receiving daily recess, the teacher's rating of class behavior scores did not differ significantly according to the level of exposure. CONCLUSIONS:These results indicated that, among 8- to 9-year-old children, having > or =1 daily recess period of >15 minutes in length was associated with better teacher's rating of class behavior scores. This study suggests that schoolchildren in this age group should be provided with daily recess.