28 research outputs found
Maturation of the Cardiac Autonomic Nervous System Activity in Children and Adolescents
Background
Despite the increasing interest in cardiac autonomic nervous activity, the normal development is not fully understood. The main aim was to determine the maturation of different cardiac sympatheticâ(SNS) and parasympathetic nervous system (PNS) activity parameters in healthy patients aged 0.5 to 20 years. A second aim was to determine potential sex differences.
Methods and Results
Five studies covering the 0.5â to 20âyear age range provided impedanceâ and electrocardiography recordings from which heart rate, different PNSâparameters (eg, respiratory sinus arrhythmia) and an SNSâparameter (preâejection period) were collected. Age trends were computed in the mean values across 12 ageâbins and in the ageâspecific variances. Age was associated with changes in mean and variance of all parameters. PNSâactivity followed a cubic trend, with an exponential increase from infancy, a plateau phase during middle childhood, followed by a decrease to adolescence. SNSâactivity showed a more linear trend, with a gradual decrease from infancy to adolescence. Boys had higher SNSâactivity at ages 11 to 15 years, while PNSâactivity was higher at 5 and 11 to 12 years with the plateau level reached earlier in girls. Interindividual variation was high at all ages. Variance was reasonably stable for SNSâ and the logâtransformed PNSâparameters.
Conclusions
Cardiac PNSâ and SNSâactivity in childhood follows different maturational trajectories. Whereas PNSâactivity shows a cubic trend with a plateau phase during middle childhood, SNSâactivity shows a linear decrease from 0.5 to 20 years. Despite the large samples used, clinical use of the sexâspecific centile and percentile normative values is modest in view of the large individual differences, even within narrow age bands.National Institute of Diabetes and Digestive and Kidney Diseases; the Netherlands Organization for Scientific Research; National Initiative for Brain and Cognition Research; European Commission under the 7th Framework Health Program with Grant; The Netherlands Organization for Health Research and Development (ZonMw); The Dutch Heart Foundatio
Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease
Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 Ă 10â10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 Ă 10â10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis