Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

BACKGROUND AND OBJECTIVES: Genetic testing is recommended for individuals with autism spectrum disorder (ASD). Pathogenic yield varies by clinician and/or patient characteristics. Our objectives were to determine the pathogenic yield of genetic testing, the variability in rate of pathogenic results based on subject characteristics, and the percentage of pathogenic findings resulting in further medical recommendations in toddlers with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ASD. METHODS:We conducted a retrospective chart review of 500 toddlers, 18 to 36 months, diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (mean age: 25.8 months, 79% male). Subject demographics, medical and neuropsychological characteristics, and genetic test results were abstracted. Genetic results were divided into negative or normal, variants of unknown significance, and pathogenic. Subject characteristics were compared across results. Manual chart review determined if further recommendations Drs Harris, Barbaresi and Harstad conceptualized and designed the study; Dr Harris designed the data collection instruments, collected data, and drafted the initial manuscript; Dr Sideridis conducted the statistical analyses and reviewed and revised the manuscript; Drs Harris, Sideridis, Barbaresi, and Harstad reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Purpose: We describe a novel neurobehavioral syndrome of autism spectrum disorder, intellectual disability, and attention deficit/hyperactivity disorder associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods: We assembled a cohort of 36 individuals (from 31 unrelated families) with de novo mutations in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results: These individuals share neurobehavioral features including autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD); other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion: These results establish deleterious variation in RFX3, RFX4, and RFX7 as important causes of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.

No abstract

Background: Deliberate practice facilitates skill mastery. We aimed to create a novel resident-as-teacher rotation, leveraging a deliberate practice framework with repeated practice in real-life teaching settings, with feedback from dedicated faculty member coaches. Methods: A resident-as-teacher rotation was designed for 35 Postgraduate Year-2 (PGY2) paediatric residents. To facilitate deliberate practice, teaching experiences were observed by faculty member coaches and were repeated with different audiences. Participating residents received pre-rotation, post-rotation and follow-up surveys on their

No abstract

Neurodevelopmental disorders (NDDs) are frequently associated with gastrointestinal symptoms (GIS) and sleep issues, but there are insufficient data on the occurrence of these symptoms in young children with autism spectrum disorder (ASD) compared with other NDDs. We abstracted data on 500 children aged 18 to 36 months with ASD and 146 children aged 18 to 47 months with non-ASD NDDs to compare the frequency of these symptoms. In the overall sample, there was a high rate of GIS (46.0%) and sleep difficulties (22.6%). In age-adjusted analyses, children with non-ASD NDDs were more likely to have GIS (61.0% vs 41.6%; adjusted odds ratio [OR] = 2.35; 95% confidence interval = 1.56-3.56) and sleep difficulties (34.9% vs 19.0%; adjusted OR = 2.08; 95% confidence interval = 1.33-3.26) compared with those with ASD. These findings demonstrate the need to assess these symptoms in all young children with developmental concerns to provide appropriate guidance to their families.

Background: Dacryocystitis is considered benign, yet infants represent a population at risk of complications. The presentation, management, and rates of serious bacterial infection in infants with dacryocystitis have not been described. Methods: We conducted a retrospective study of infants (12 months or younger) presenting to a single urban tertiary care pediatric emergency department between January 1995 and March 2014 with concern for dacryocystitis. Exclusion criteria included immune compromise or craniofacial anomalies. Cases were identified using text search software, followed by manual chart review. Results: We identified 333 subjects, and median age was 38 days (interquartile range, 12; 106). Fifty-three percent were female. Most were afebrile (81%, T < 38°C) at triage while 6% had fever of ≥39°C. Two of 135 blood cultures sent were positive (both Streptococcus pneumoniae). Lumbar punctures were performed on 40 patients (12%), and no cerebrospinal fluid (CSF) cultures were positive. Eye cultures were positive in 47% (N = 58) of infants cultured (N = 123); the most common pathogens were Haemophilus species (N = 17), Staphylococcus aureus (N = 13), Gram-negative rods (N = 7), and Moraxella species (N = 4). Imaging was obtained in 11 subjects (3.3%) with 3 demonstrating cellulitis and 1 a hemangioma. Ophthalmology was consulted for 21%, and an intervention/probe performed in 6%. Topical antibiotics were used in 147 subjects (44%), oral antibiotics in 100 (33%), and parenteral antibiotics in 87 (26%). Conclusion: Infants with dacryocystitis have a variable presentation and management ranges from observation to aggressive management. The rates of serious bacterial infection were low in this sample and not associated with any presenting risk factors.