De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies

Congenital heart disease (CHD) patients have an increased prevalence of extracardiac congenital anomalies (CAs) and risk of neurodevelopmental disabilities (NDDs). Exome sequencing of 1213 CHD parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in the developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD, and CA but only 2% of patients with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, a regulator of mRNA splicing. Genes mutated in other cohorts examined for NDD were enriched in CHD cases, particularly those with coexisting NDD. These findings reveal shared genetic contributions to CHD, NDD, and CA and provide opportunities for improved prognostic assessment and early therapeutic intervention in CHD patients

De novo mutations in histone modifying genes in congenital heart disease

Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging mutations. Similar odds ratios were seen across major classes of severe CHD. We found a marked excess of de novo mutations in genes involved in production, removal or reading of H3K4 methylation (H3K4me), or ubiquitination of H2BK120, which is required for H3K4 methylation2–4. There were also two de novo mutations in SMAD2; SMAD2 signaling in the embryonic left-right organizer induces demethylation of H3K27me5. H3K4me and H3K27me mark `poised' promoters and enhancers that regulate expression of key developmental genes6. These findings implicate de novo point mutations in several hundred genes that collectively contribute to ~10% of severe CHD

De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies

Congenital heart disease (CHD) patients have an increased prevalence of extracardiac congenital anomalies (CAs) and risk of neurodevelopmental disabilities (NDDs). Exome sequencing of 1213 CHD parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in the developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD, and CA but only 2%of patients with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, a regulator ofmRNA splicing. Genes mutated in other cohorts examined for NDD were enriched in CHD cases, particularly those with coexisting NDD. These findings reveal shared genetic contributions to CHD, NDD, and CA and provide opportunities for improved prognostic assessment and early therapeutic intervention in CHD patients

Health implications of new age technologies for adolescents: a review of the research

PURPOSE OF REVIEW: Within the past 20 years, there have been profound advances in personal technology. Although adolescents have embraced the Internet, video games and smart phones, with their extraordinary potential for education, entertainment and connecting with peers, respectively, there is a \u27dark side\u27 to these new age technologies. This article identifies many of the adverse physical, psychological, developmental and emotional consequences of our new age technologies. RECENT FINDINGS: As Internet access has become easier, faster and more ubiquitous, there is increased evidence of its potential for direct and indirect harm to teens. Sexually explicit material is now indiscriminately available to youth, and studies have linked pornography with a number of negative health effects. Internet addiction is a problem even among teenagers who do not view pornography online. The rise of the Internet and social media sites now makes it easier for a student to bully a peer, and adolescents represent the majority of cyberbullying victims These technologies not only carry increased morbidity but also mortality, with increased suicides due to cyberbullying and motor vehicle deaths due to texting while driving. SUMMARY: Paediatricians play a critical role in educating adolescents and their parents about the risks associated with new age technologies

Adolescent consumption of sports drinks

Copyright © 2018 by the American Academy of Pediatrics. BACKGROUND: Sports drinks are aggressively marketed to teenagers to replenish fluids and/or electrolytes. According to the American Academy of Pediatrics, typical adolescent physical activity does not require sports drink rehydration. Given US obesity rates and that sugar-sweetened sports drinks add superfluous calories to the diet, it is important to assess adolescent sports drink consumption and changes over time. METHODS: Researchers in the 2015 Youth Risk Behavior Survey and 2010 National Youth Physical Activity and Nutrition Survey collected nationally representative samples of US high school students about sports drink consumption. Respondent characteristics and health behaviors were examined relative to sports drink consumption by using multivariable survey logistic regression. ?2tests were used to compare the 2 samples and examine changes over time. RESULTS: The 2015 Youth Risk Behavior Survey and 2010 National Youth Physical Activity and Nutrition Survey had national samples of 15624 and 11458 respondents, respectively. Sports drink consumption in the previous week increased from 56% (2010) to 57.6% (2015; P= .0002). However, comparisons of daily sports drink consumption revealed reductions for all age groups, sexes, race and/or ethnicity categories, and levels of physical activity. The greatest reductions were for non-Hispanic African Americans and for children with overweight. Daily sports drink consumption did not decrease for children with obesity and increased for children who watched \u3e2 hours per day of television. In 2015, boys, non-Hispanic African Americans, Hispanics, and tobacco users exhibited higher odds of consuming sports drinks daily. CONCLUSIONS: Although daily consumption of sports drinks has decreased overall, sugar-sweetened sports drinks remain popular, with the majority of high school students drinking them at least weekly. Of concern, daily consumption increased among teenagers watching television \u3e2 hours per day. Pediatricians should counsel adolescents about the American Academy of Pediatrics’ recommendations regarding sports drinks

Pediatricians\u27 knowledge, attitudes and practices surrounding menstruation and feminine products

© 2020 Walter de Gruyter GmbH, Berlin/Boston. This study investigates whether primary care pediatricians adhere to the American Academy of Pediatrics (AAP) recommendations by routinely evaluating patients\u27 menstrual cycles and educating patients about menstruation and feminine products. Additionally, this study examines pediatricians\u27 knowledge and attitudes surrounding menstrual health topics. A 53-item online questionnaire was developed to evaluate pediatricians\u27 knowledge, attitudes and clinical practices regarding menstruation-related topics. The questionnaire was emailed to 2500 AAP members using a geographically-stratified sampling approach, with pediatricians in each state selected randomly. Mann-Whitney U tests, t-tests, and logistic regressions were used to assess associations between correlates and pediatricians\u27 knowledge, attitudes and practices. Five hundred and eighteen out of 2500 pediatricians participated (response rate = 20.7%), 462 met inclusion criteria; 78.8% were female, 79.2% were Caucasian. The majority of the pediatricians (58.2%) were not at all or only slightly familiar with the AAP guidelines on anticipatory guidance surrounding menarche. Many reported they do not routinely provide anticipatory guidance regarding menstruation to pre-menarchal patients (24.7%), discuss menstruation with post-menarchal patients (33.1%) or ask patients the date of their last period (28.4%). The majority were unlikely to discuss feminine products with patients. Gaps in menstruation-related knowledge were noted. Male pediatricians were significantly less likely to evaluate patients\u27 menstrual cycles and provide patient-education regarding menstruation-related topics, and had significantly lower self-rated and measured knowledge of these topics. A concerning number of pediatricians in a national sample do not abide by AAP recommendations surrounding menstruation and exhibit knowledge gaps in this area. To effectively address the health needs of female patients, pediatricians should better incorporate menstrual health care into their clinical practice