Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features.

SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system. Despite its important developmental roles, SOX5 disruption has yet to be associated with human disease. We report one individual with a reciprocal translocation breakpoint within SOX5, eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent), and seven individuals with larger 12p12 deletions encompassing SOX5. Common features in these subjects include prominent speech delay, intellectual disability, behavior abnormalities, and dysmorphic features. The phenotypic impact of the deletions may depend on the location of the deletion and, consequently, which of the three major SOX5 protein isoforms are affected. One intragenic deletion, involving only untranslated exons, was present in a more mildly affected subject, was inherited from a healthy parent and grandparent, and is similar to a deletion found in a control cohort. Therefore, some intragenic SOX5 deletions may have minimal phenotypic effect. Based on the location of the deletions in the subjects compared to the controls, the de novo nature of most of these deletions, and the phenotypic similarities among cases, SOX5 appears to be a dosage-sensitive, developmentally important gene.

Peer victimization in youth with Tourette syndrome and other chronic tic disorders.

Chronic tic disorders including Tourette syndrome have negative impact across multiple functional domains. We explored associations between peer victimization status and tic subtypes, premonitory urges, internalizing symptoms, explosive outbursts, and quality of life among youth with chronic tic disorders, as part of the internet-based omnibus Tourette Syndrome Impact Survey. A mixed methods design combined child self-report and parental proxy-report (i.e., parent reporting on the child) demographic and quantitative data for affected youth ages 10-17 years addressing gender, mean age, ethnicity and other socioeconomic features, and presence of tic disorders and co-occurring psychiatric disorders. Peer "Victim" versus "Non-victim" status was determined using a subset of four questions about being bullied. "Victim" status was identified for those youth who endorsed the frequency of the occurrence of being bullied in one or more of the four questions as "most of the time" or "all of the time". Data from 211 eligible youth respondents and their parents/guardians showed 26% reporting peer victimization. Victim status was associated with greater tic frequency, complexity and severity; explosive outbursts; internalizing symptoms; and lower quality of life. Peer victimization among youth with chronic tic disorders is common and appears associated with tic morbidity, anxiety, depression, explosive outbursts, and poorer psychosocial functioning. Anticipatory guidance, specific bullying screening and prevention, and further studies are indicated in this population.

Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity.

PURPOSE: The short arm of chromosome 16 is rich in segmental duplications, predisposing this region of the genome to a number of recurrent rearrangements. Genomic imbalances of an approximately 600-kb region in 16p11.2 (29.5-30.1 Mb) have been associated with autism, intellectual disability, congenital anomalies, and schizophrenia. However, a separate, distal 200-kb region in 16p11.2 (28.7-28.9 Mb) that includes the SH2B1 gene has been recently associated with isolated obesity. The purpose of this study was to better define the phenotype of this recurrent SH2B1-containing microdeletion in a cohort of phenotypically abnormal patients not selected for obesity. METHODS: Array comparative hybridization was performed on a total of 23,084 patients in a clinical setting for a variety of indications, most commonly developmental delay. RESULTS: Deletions of the SH2B1-containing region were identified in 31 patients. The deletion is enriched in the patient population when compared with controls (P = 0.003), with both inherited and de novo events. Detailed clinical information was available for six patients, who all had developmental delays of varying severity. Body mass index was ≥95th percentile in four of six patients, supporting the previously described association with obesity. The reciprocal duplication, found in 17 patients, does not seem to be significantly enriched in our patient population compared with controls. CONCLUSIONS: Deletions of the 16p11.2 SH2B1-containing region are pathogenic and are associated with developmental delay in addition to obesity.

Bullying and school safety.

OBJECTIVE: To identify an association between involvement in bullying and problems in school. STUDY DESIGN: This was a cross-sectional study of 5391 students in grades 7, 9, and 11 in an urban public school district. The main outcome measure was involvement in bullying. Secondary outcomes included attendance, grade point average, psychosocial distress, and perceived acceptability of carrying guns to school. RESULTS: Of the 5391 children surveyed, 26% were involved in bullying either as victim, bully, or both (bully-victim). All 3 groups were significantly more likely than bystanders to feel unsafe at school and sad most days. Victims and bully-victims were more likely to say they are "no good." Victims were more likely to feel that they "do not belong" in their school. The odds of being a victim (vs a bystander) were 10% lower for every 1 point increase in grade point average. Bully-victims were more likely to say that it is "not wrong" to take a gun to school. CONCLUSIONS: Associations between involvement in bullying and academic achievement, psychological distress, and the belief that it is not wrong to take a gun to school reinforce the notion that school environment is interrelated with mental health and school success.

Early cognitive stimulation, emotional support, and television watching as predictors of subsequent bullying among grade-school children.

BACKGROUND: Bullying is a major public health issue, the risk factors for which are poorly understood. OBJECTIVE: To determine whether cognitive stimulation, emotional support, and television viewing at age 4 years are independently associated with being a bully at ages 6 through 11 years. METHODS: We used multivariate logistic regression, using data from the National Longitudinal Survey of Youth, to adjust for multiple confounding factors. RESULTS: Parental cognitive stimulation and emotional support at age 4 years were each independently protective against bullying, with a significant odds ratio of 0.67 for both variables associated with a 1-SD increase (95% confidence interval, 0.54-0.82 for cognitive stimulation and 0.54-0.84 for emotional support). Each hour of television viewed per day at age 4 years was associated with a significant odds ratio of 1.06 (95% confidence interval, 1.02-1.11) for subsequent bullying. These findings persisted when we controlled for bullying behavior at age 4 years in a subsample of children for whom this measure was available. CONCLUSION: The early home environment, including cognitive stimulation, emotional support, and exposure to television, has a significant impact on bullying in grade school.

Bullying, psychosocial adjustment, and academic performance in elementary school.

BACKGROUND: Over the past decade, concerns about bullying and its role in school violence, depression, and health concerns have grown. However, no large studies in the United States have examined the prevalence of bullying during elementary school or its association with objective measures of school attendance and achievement. OBJECTIVE: To determine the prevalence of bullying during elementary school and its association with school attendance, academic achievement, disciplinary actions, and self-reported feelings of sadness, safety, and belonging. DESIGN: Cross-sectional study using 2001-2002 school data. SETTING: Urban, West Coast public school district. PARTICIPANTS: Three thousand five hundred thirty (91.4%) third, fourth, and fifth grade students. MAIN OUTCOME MEASURE: Self-reported involvement in bullying. RESULTS: Twenty-two percent of children surveyed were involved in bullying either as a victim, bully, or both. Victims and bully-victims were more likely to have low achievement than bystanders (odds ratios [ORs], 0.8 [95% confidence interval (CI), 0.7-0.9] and 0.8 [95% CI, 0.6-1.0], respectively). All 3 bullying-involved groups were significantly more likely than bystanders to feel unsafe at school (victims, OR, 2.1 [95% CI, 1.1-4.2]; bullies, OR, 2.5 [95% CI, 1.5-4.1]; bully-victims, OR, 5.0 [95% CI, 1.9-13.6]). Victims and bully-victims were more likely to report feeling that they don't belong at school (ORs, 4.1 [95% CI, 2.6-6.5] and 3.1 [95% CI, 1.3-7.2], respectively). Bullies and victims were more likely than bystanders to feel sad most days (ORs 1.5 [95% CI, 1.2-1.9] and 1.8 [95% CI, 1.2-2.8], respectively). Bullies and bully-victims were more likely to be male (ORs, 1.5 [95% CI, 1.2-1.9] and 3.0 [95% CI, 1.3-7.0], respectively). CONCLUSIONS: The prevalence of frequent bullying among elementary school children is substantial. Associations between bullying involvement and school problems indicate this is a serious issue for elementary schools. The research presented herein demonstrates the need for evidence-based antibullying curricula in the elementary grades.