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Abstract Background This cross-sectional controlled study aims to assess health-related quality of life (HRQoL) of children and adolescents with a molecular diagnosis of Marfan syndrome (MFS) or related disorders and to evaluate the factors associated with HRQoL in this population. Sixty-three children with MFS and 124 age- and sex-matched healthy children were recruited. HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL™) generic questionnaire. The correlation between HRQoL scores and the different continuous parameters (age, body mass index, disease severity, systemic score, aortic sinus diameter, and aerobic physical capacity) was evaluated using Pearson’s or Spearman’s coefficient. A multiple linear regression analysis was performed on the two health summary self-reported PedsQL™ scores (physical and psychosocial) to identify the factors associated with HRQoL in the MFS group. Results Except for emotional functioning, all other domains of HRQoL (psychosocial and physical health, social and school functions) were significantly lower in children with MFS compared to matched healthy children. In the MFS group, the physical health summary score was significantly lower in female than in male patients (self-report: absolute difference [95%CI] = -8.7 [-17.0; -0.47], P = 0.04; proxy-report: absolute difference [95%CI] = -8.6 [-17.3; 0.02], P = 0.05) and also negatively correlated with the systemic score (self-report: R = -0.24, P = 0.06; proxy-report: R = -0.29, P = 0.03) and with the height Z-score (proxy-report: R = -0.29, P = 0.03). There was no significant difference in the physical health summary scores between the different genetic subgroups. In the subgroup of 27 patients who performed a cardiopulmonary exercise test, self- and proxy-reported physical health summary scores were highly correlated with their aerobic physical capacity assessed by peak oxygen consumption (VO2max) and ventilatory anaerobic threshold (VAT). In the multivariate analysis, the most important independent predictors of decreased physical health were increased height, decreased body mass index, decreased VAT and use of prophylactic therapy. Conclusions This study reports an impaired HRQoL in children and adolescents with MFS or related conditions, in comparison with matched healthy children. Educational and rehabilitation programs must be developed and evaluated to improve exercise capacity and HRQoL in these patients. Trial registration ClinicalTrials.gov, NCT03236571 . Registered 28 July 2017.

Abstract While 3D chromatin organization in topologically associating domains (TADs) and loops mediating regulatory element-promoter interactions is crucial for tissue-specific gene regulation, the extent of their involvement in human Mendelian disease is largely unknown. Here, we identify 7 families presenting a new cardiac entity associated with a heterozygous deletion of 2 CTCF binding sites on 4q25, inducing TAD fusion and chromatin conformation remodeling. The CTCF binding sites are located in a gene desert at 1 Mb from the Paired-like homeodomain transcription factor 2 gene (PITX2). By introducing the ortholog of the human deletion in the mouse genome, we recapitulate the patient phenotype and characterize an opposite dysregulation of PITX2 expression in the sinoatrial node (ectopic activation) and ventricle (reduction), respectively. Chromatin conformation assay performed in human induced pluripotent stem cell-derived cardiomyocytes harboring the minimal deletion identified in family#1 reveals a conformation remodeling and fusion of TADs. We conclude that TAD remodeling mediated by deletion of CTCF binding sites causes a new autosomal dominant Mendelian cardiac disorder.

AimsPediatric transoesophageal echocardiography (TOE) probes have remained two-dimensional (2D) limiting their use compared to adults. While critical in pediatrics for interventions and post-surgery assessments, technological advancements introduced a three-dimensional (3D) pediatric TOE probe. This study assessed the new 3D pediatric TOE probe (GE 9VT-D) for feasibility, handling, and imaging quality.Methods and resultsAt Children's Hospital of Toulouse, 2-month prospective study enrolled children undergoing TOE with the new probe. All imaging modalities were rated by 2 operators using a 5-point Likert-type scale from 1 (very poor) to 5 (very good) quality. Forty-five children, median age 3.7 (range: 2 months-14.7 years) median weight 7.8 kg (range: 4.3–48 kg) underwent 60 TOEs: 25% pre-surgery, 45% post-surgery, 28% during percutaneous procedures, and 2% in intensive care. Probe handling was “very easy” in all cases without adverse events. The median score of 2D, 2D colour, pulsed Doppler and 3D were noted 5 out of 5 and continuous Doppler and 3D colour 4 out of 5. The 3D image quality remained consistent irrespective of the patient weighing above or below 7.8 kg (p = 0.72). Postoperative TOEs identified two cases needing further interventions, emphasizing its value in evaluating surgical outcomes and also for guiding percutaneous interventions.ConclusionOur comprehensive evaluation demonstrates that the new 3D pediatric TOE probe is feasible and provides high-quality imaging in pediatric patients. The successful integration of this novel probe into clinical practice has the potential to enhance diagnostic accuracy and procedural planning, ultimately optimizing patient outcomes in pediatric cardiac care.

BackgroundPaediatric interventional catheterisation has consistently improved in recent decades, with often highly successful outcomes. However, progress is still required in terms of the information delivered to parents and how parental anxiety is managed.AimTo investigate the impact of cardiac printed models on improving parental understanding and alleviating anxiety before interventional catheterisation.MethodsThe parents of children undergoing interventional cardiac catheterisation were prospectively enrolled in the study. A questionnaire highlighting knowledge and understanding of the condition and cardiac catheterisation per se was scored on a scale of 1–30. The State-Trait Anxiety Inventory (STAI), which generates current anxiety scores, was also used before and after the pre-catheterisation meeting. The “printing group” received an explanation of catheterisation using the device and a three-dimensional (3D) model, while the “control group” received an explanation using only the device and a manual drawing.ResultsIn total, 76 parents of 50 children were randomly assigned to a “control group” (n = 38) or “printing group” (n = 38). The groups were comparable at baseline. The level of understanding and knowledge improved after the “control group” and “printing group” meetings (+5.5±0.8 and +10.2±0.8; p