Growth patterns in fetuses with isolated cardiac defects

Objectives: There is evidence that in fetuses with congenital heart defects (CHDs), head growth is affected. However, scanty data are available on longitudinal growth patterns of other biometric parameters such as abdominal circumference (AC) and femur length (FL). The aim was to evaluate growth patterns in fetuses with isolated CHD diagnosed prenatally in different categories of lesions. Methods: Fetuses with isolated CHD seen between 2008 and 2013 at the Fetal Medicine Unit of 2 tertiary referral centers were retrospectively included in the study. CHD was classified into 7 categories. Fetal biometry parameters were assessed at 4 variable time points between 18 and 35 weeks' gestation and transformed into Z scores. Linear mixed modeling was performed to analyze repeated measurements and construction of growth models. Results: Two hundred forty-six live births with CHD were analyzed. Linear growth modeling showed a slight decrease in head circumference (HC) in the second half of pregnancy, whereas AC and FL growth were not significantly affected. The model predicted a significantly smaller HC at 36 weeks' gestation in fetuses with conotruncal heart defects. Conclusions: Fetuses with CHD showed a modest but significant linear decrease in HC growth, whereas AC and FL growth trajectories remained stable

Paediatric Ebstein's anomaly: How clinical presentation predicts mortality

Background Forecasting the prognosis of a child when diagnosed with Ebstein's anomaly is difficult. We, therefore, studied which factors at the time of diagnosis are associated with death during childhood. Methods All consecutive patients (0-18 years) diagnosed with Ebstein's anomaly in the Netherlands between 1980 and 2014 were included. Survival curves were obtained using the Kaplan-Meier method. By using the Cox proportional hazard model, we analysed the factors (at diagnosis) that were associated with death. Results We included 176 patients. Thirty-one patients (18%) died before the age of 18 years. The 1-year survival was 84% and remained stable at 82% from 35 months after diagnosis and onwards. Modified Ross Heart Failure Class 4 at the time of diagnosis was the most important risk factor for death during childhood (HR 12.5, 95% CI 4.4 to 35.9). Furthermore, diagnosis in the neonatal period (HR 4.2, 95% CI 1.5 to 12.0), severe tricuspid valve regurgitation (HR 2.4, 95% CI 1.2 to 5.0), severe right ventricular outflow tract obstruction (HR 3.7, 95% CI 1.8 to 7.7) and a patent ductus arteriosus (HR 2.8, 95% CI 1.3 to 6.0) at the time of diagnosis were univariately associated with death. Multivariable analysis showed that presentation with Heart Failure Class 4 and a ventricular septal defect is the strongest predictor of death in childhood and adolescence. Conclusion Patients with Ebstein's anomaly presenting with Heart Failure Class 4 and a ventricular septal defect have a high risk of death during childhood

Erratum: Feasibility and predictors of change of narrative exposure therapy for displaced populations: A repeated measures design (Pilot and Feasibility Studies (2020) 6 (69) DOI: 10.1186/s40814-020-00613-1)

Following publication of the original article [1], the authors reported an error in the following sentence: Studies into TFT for non-refugee traumatized populations show higher effects (d = 1.08—1.40) [7], than for refugee populations (g = .25—1.01) [8]. Which will be replaced by: There is evidence that non-refugee traumatized populations benefit more from TFT than traumatized groups with a refugee background [7, 8]. This also involves changes in reference [8]. “Turrini, G., Purgato, M., Acarturk, C., Anttila, M., Au, T., Ballette, F., ... & Hall, J. (2019). Efficacy and acceptability of psychosocial interventions in asylum seekers and refugees: systematic review and meta-analysis. Epidemiology and psychiatric sciences, 28(4), 376– 388.doi.org/10.1017/S2045796019000027”. should replace: “Lambert JE, Alhassoon OM. Trauma-focused therapy for refugees: Meta-analytic findings. Journal of counseling psychology. 2015;62(1):28. DOI: 10.1037/cou0000048”. The publishers apologise for this error

Surgical outcome in pediatric patients with Ebstein's anomaly: A multicenter, long-term study

Surgical outcomes of pediatric patients with Ebstein's anomaly are often described as part of all-age-inclusive series. Our objective is to focus on patients treated surgically in childhood (0-18 y). We study the intended treatment (biventricular or 1.5 ventricle repair or univentricular palliation), freedom from unplanned reoperation and survival of this specific age group, in a nationwide study. Records of all Ebstein's anomaly patients born between 1980 and 2013 were reviewed. Demographic variables, intraoperative procedures and postoperative outcomes were analyzed. Sixty-three patients underwent 109 operations. Median follow-up after diagnosis was 121 months (range 0-216 months). Twenty-nine (46%) patients required surgery in the first year of life, including 21 who required neonatal surgery. The intended treatment was biventricular (n = 37, 59%) and 1.5 ventricle (n = 5, 8%) repair or univentricular (n = 21, 33%) palliation. The one-, five-, and 10-year freedom from unplanned reoperation was 89%, 79%, and 75% respectively. There were nine (14%) in hospital deaths (within 30 d after surgery). Causes of death were low cardiac output syndrome, cardiac failure, hypoxemia, pulmonary hypertension or an unknown cause. There were no late deaths. Surgery in childhood represents the worse spectrum of disease, biventricular repair is often not applied. Patients often face revision surgery. Mortality is limited to the immediate postsurgical perio

Biallelic Variants in ASNA1, Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy

BACKGROUND: Pediatric cardiomyopathies are a clinically and genetically heterogeneous group of heart muscle disorders associated with high morbidity and mortality. Although knowledge of the genetic basis of pediatric cardiomyopathy has improved considerably, the underlying cause remains elusive in a substantial proportion of cases. METHODS: Exome sequencing was used to screen for the causative genetic defect in a pair of siblings with rapidly progressive dilated cardiomyopathy and death in early infancy. Protein expression was assessed in patient samples, followed by an in vitro tail-anchored protein insertion assay and functional analyses in zebrafish. RESULTS: We identified compound heterozygous variants in the highly conserved ASNA1 gene (arsA arsenite transporter, ATP-binding, homolog), which encodes an ATPase required for post-translational membrane insertion of tail-anchored proteins. The c.913C>T variant on the paternal allele is predicted to result in a premature stop codon p.(Gln305*), and likely explains the decreased protein expression observed in myocardial tissue and skin fibroblasts. The c.488T>C variant on the maternal allele results in a valine to alanine substitution at residue 163 (p.Val163Ala). Functional studies showed that this variant leads to protein misfolding as well as less effective tail-anchored protein insertion. Loss of asna1 in zebrafish resulted in reduced cardiac contractility and early lethality. In contrast to wild-type mRNA, injection of either mutant mRNA failed to rescue this phenotype. CONCLUSIONS: Biallelic variants in ASNA1 cause severe pediatric cardiomyopathy and early death. Our findings point toward a critical role of the tail-anchored membrane protein insertion pathway in vertebrate cardiac function and disease

Biallelic Variants in ASNA1, Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy

BACKGROUND: Pediatric cardiomyopathies are a clinically and genetically heterogeneous group of heart muscle disorders associated with high morbidity and mortality. Although knowledge of the genetic basis of pediatric cardiomyopathy has improved considerably, the underlying cause remains elusive in a substantial proportion of cases. METHODS: Exome sequencing was used to screen for the causative genetic defect in a pair of siblings with rapidly progressive dilated cardiomyopathy and death in early infancy. Protein expression was assessed in patient samples, followed by an in vitro tail-anchored protein insertion assay and functional analyses in zebrafish. RESULTS: We identified compound heterozygous variants in the highly conserved ASNA1 gene (arsA arsenite transporter, ATP-binding, homolog), which encodes an ATPase required for post-translational membrane insertion of tail-anchored proteins. The c.913C>T variant on the paternal allele is predicted to result in a premature stop codon p.(Gln305*), and likely explains the decreased protein expression observed in myocardial tissue and skin fibroblasts. The c.488T>C variant on the maternal allele results in a valine to alanine substitution at residue 163 (p.Val163Ala). Functional studies showed that this variant leads to protein misfolding as well as less effective tail-anchored protein insertion. Loss of asna1 in zebrafish resulted in reduced cardiac contractility and early lethality. In contrast to wild-type mRNA, injection of either mutant mRNA failed to rescue this phenotype. CONCLUSIONS: Biallelic variants in ASNA1 cause severe pediatric cardiomyopathy and early death. Our findings point toward a critical role of the tail-anchored membrane protein insertion pathway in vertebrate cardiac function and disease