Studies in patients with childhood-onset end-stage renal disease (ESRD) provide a diagnostic window to the evolution of cardiovascular disease (CVD) in this population. Hyperphosphataemia and renal osteodystrophy are particularly difficult to treat in paediatric patients, but there is only limited information regarding the effect of calcium-containing phosphate binders and vitamin D preparations on the development of CVD in the young. We studied 40 adult patients (mean age 23.6 years) who developed ESRD at the age of 11.5 +/- 4 years and 40 matched healthy control subjects. Nine patients were on dialysis and 31 had a functioning kidney transplant. Measurements included intima-media thickness (IMT) of the common carotid artery, electron beam computed tomography (EBCT) for the detection of coronary artery calcifications (CAC), echocardiography and post-ischaemic arterial blood flow by venous occlusion plethysmography. Patient characteristics, atherosclerotic risk factors and a complete account of prescribed medications were analysed for correlations with arterial and cardiac changes. The IMT was not significantly different in patients and controls; four patients (10%) had coronary calcifications on EBCT. Twenty-five patients (62.5%) had left ventricular hypertrophy. Patients had a 40% reduction of post-ischaemic arterial flow. Morphological alterations of the heart and arteries were significantly correlated with the duration of ESRD and dialysis time, and with the cumulative intake of calcium-containing phosphate binders and active vitamin D preparations. Functional changes (vascular reactivity) were correlated with duration of ESRD and non-traditional risk factors. Young adults with ESRD since childhood have systemic CVD characterized by a decrease in arterial elasticity, the occurrence of CAC and changes in left ventricular morphology. Treatment with calcium-containing phosphate binders and active vitamin D preparations is independently associated in a dose-dependent manner with surrogate markers for CVD.

Background: Myocarditis is one of the most common causes leading to heart failure in children and a possible genetic background has been postulated. We sought to characterize the clinical and genetic characteristics in patients with myocarditis ≤18 years of age to predict outcome. Methods: A cohort of 42 patients (Genetics in Pediatric Myocarditis) with biopsy-proven myocarditis underwent genetic testing with targeted panel sequencing of cardiomyopathy-associated genes. Genetics in Pediatric Myocarditis patients were divided into subgroups according to the phenotype of dilated cardiomyopathy (DCM) at presentation, resulting in 22 patients without DCM (myocarditis without phenotype of DCM) and 20 patients with DCM (myocarditis with phenotype of DCM). Results: Myocarditis with phenotype of DCM patients (median age 1.4 years) were younger than myocarditis without phenotype of DCM patients (median age 16.1 years; P <0.001) and were corresponding to heart failure–like and coronary syndrome–like phenotypes, respectively. At least one likely pathogenic/pathogenic variant was identified in 9 out of 42 patients (22%), 8 of them were heterozygous, and 7 out of 9 were in myocarditis with phenotype of DCM. Likely pathogenic/pathogenic variants were found in genes validated for primary DCM ( BAG3, DSP, LMNA, MYH7, TNNI3, TNNT2 , and TTN ). Rare variant enrichment analysis revealed significant accumulation of high-impact disease variants in myocarditis with phenotype of DCM versus healthy individuals ( P =0.0003). Event-free survival was lower ( P =0.008) in myocarditis with phenotype of DCM patients compared with myocarditis without phenotype of DCM and primary DCM. Conclusions: We report heterozygous likely pathogenic/pathogenic variants in biopsy-proven pediatric myocarditis. Myocarditis patients with DCM phenotype were characterized by early-onset heart failure, significant enrichment of likely pathogenic/pathogenic variants, and poor outcome. These phenotype-specific and age group–specific findings will be useful for personalized management of these patients. Genetic evaluation in children newly diagnosed with myocarditis and DCM phenotype is warranted.

Background: Long-QT syndrome (LQTS) causes a prolongation of the QT-interval in the ECG leading to life threatening tachyarrhythmia and ventricular fibrillation. One atypical form of LQTS, Timothy syndrome (TS), is associated with syndactyly, immune deficiency, cognitive and neurological abnormalities as well as distinct cranio-facial abnormalities. Case presentation: On a family with both children diagnosed with clinical LQTS, we performed whole exome sequencing to comprehensively screen for causative mutations after a targeted candidate gene panel screen for Long-QT syndrome target genes failed to identify any underlying genetic defect. Using exome sequencing, we identified in both affected children, a p.402G > S mutation in exon 8 of the CACNA1C gene, a voltage-dependent Ca²⁺ channel. The mutation was inherited from their father, a mosaic mutation carrier. Based on this molecular finding and further more careful clinical examination, we refined the diagnosis to be Timothy syndrome (TS2) and thereby were able to present new therapeutic approaches. Conclusions: Our study highlights the difficulties in accurate diagnosis of patients with rare diseases, especially those with atypical clinical manifestation. Such challenge could be addressed with the help of comprehensive and unbiased mutation screening, such as exome sequencing.

Agenesis of the superior vena cava is a rare anomaly that is generally asymptomatic in the neonate. We report a male neonate with bilateral (total) agenesis of the superior vena cava with obstructed thoracic duct and subsequent congenital hydrothorax, anomalies that were detected by prenatal ultrasound at 25 weeks' gestation. The cardiac anomaly was confirmed by postnatal magnetic resonance angiography. The chylothorax disappeared with conservative therapy. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.