Homozygous loss-of-function mutations in MNS1 cause laterality defects and likely male infertility.

The clinical spectrum of ciliopathies affecting motile cilia spans impaired mucociliary clearance in the respiratory system, laterality defects including heart malformations, infertility and hydrocephalus. Using linkage analysis and whole exome sequencing, we identified two recessive loss-of-function MNS1 mutations in five individuals from four consanguineous families: 1) a homozygous nonsense mutation p.Arg242* in four males with laterality defects and infertility and 2) a homozygous nonsense mutation p.

Congenital valvular defects associated with deleterious mutations in the gene.

Background: The underlying molecular aetiology of congenital heart defects is largely unknown. The aim of this study was to explore the genetic basis of non-syndromic severe congenital valve malformations in two unrelated families.

Methods: Whole-exome analysis was used to identify the mutations in five patients who suffered from severe valvular malformations involving the pulmonic, tricuspid and mitral valves.

A human laterality disorder caused by a homozygous deleterious mutation in MMP21.

Background: Laterality in the vertebrate embryo is determined by left-right asymmetric gene expression driven by the flow of extraembryonic fluid across the embryonic node. Defects in these processes cause heterotaxy, the abnormal formation and arrangement of visceral organs that can range from complete inversion of symmetry to the selective misarrangement of organs. However, our understanding of the genetic causality for laterality defects in human beings remains relatively limited.

A human laterality disorder associated with a homozygous WDR16 deletion.

The laterality in the embryo is determined by left-right asymmetric gene expression driven by the flow of extraembryonic fluid, which is maintained by the rotary movement of monocilia on the nodal cells. Defects manifest by abnormal formation and arrangement of visceral organs. The genetic etiology of defects not associated with primary ciliary dyskinesia is largely unknown.

Conotruncal malformations and absent thymus due to a deleterious NKX2-6 mutation.

Background: Truncus arteriosus (TA) accounts for ~1% of congenital heart defects. The aetiology of isolated TA is largely unknown but when occurring as part of a syndrome, it is mostly associated with chromosome 22q11 deletion. Vice versa, the most common congenital heart defects associated with chromosome 22q11 deletion are conotruncal malformations.

Isolated truncus arteriosus associated with a mutation in the plexin-D1 gene.

Truncus arteriosus accounts for approximately 1% of congenital heart defects and the cause of isolated non-syndromic truncus arteriosus is largely unknown. In order to identify the underlying molecular defect in a consanguineous family with recurrent tuncus arteriosus, homozygosity mapping followed by whole exome sequencing was performed. This resulted in the identification of a homozygous mutation, Arg1299Cys, in the PLXND1 gene.

Prevalence of persistent superior vena cava and association with congenital heart anomalies.

A contralateral persistent superior vena cava (PSVC) can occur in a normal child or in association with congenital heart defects (CHDs). Its prevalence has been demonstrated in relatively small cohorts. We aim to assess the frequency of a PSVC in a large cohort of children with and without CHDs.

Twin pregnancy in a patient after the Fontan operation: report of a case.

Singleton pregnancy in patients with single ventricle after the Fontan operation has been reported with significant offspring and maternal complications. We report a twin pregnancy and premature delivery, in a patient following the Fontan operation.

A human laterality disorder associated with recessive CCDC11 mutation.

Background: Significant advancements in understanding the molecular pathophysiology of laterality determination were recently made. However, there are large gaps in our knowledge of the initial processes that lead to laterality defects, such as heterotaxy syndrome (HS, also known as situs ambiguous) and situs inversus totalis (SIT). The former refers to abnormal distribution of visceral organs, and the latter refers to a complete laterality inversion of both abdominal and thoracic viscera.

Intracardiac echogenic foci have no hemodynamic significance in the fetus.

Intracardiac echogenic foci (ECFs), probably representing microcalcifications of the papillary muscles, are a common finding in fetal ultrasonic screening examinations. Their significance is unclear, and their value as markers for chromosomal anomalies is debatable. It also is unknown whether ECFs predict abnormal cardiac performance.

Prevention of complete heart block in children of mothers with anti-SSA/Ro and anti-SSB/La autoantibodies: detection and treatment of first-degree atrioventricular block.

Purpose Of Review: To describe the results of two recent prospective studies that may indicate how to monitor, diagnose, and treat fetuses with neonatal lupus manifesting with heart involvement and to summarize additional research reports regarding the pathophysiology and outcomes of this rare condition.

Recent Findings: The PR Interval and Dexamethasone Evaluation study found 10 cases of neonatal lupus (10%) with three first-degree atrioventricular blocks (AVBs) and three complete heart blocks. The study included 98 pregnancies in 95 women with anti-SSA/Ro antibodies who completed weekly fetal Doppler echocardiogram-based evaluation.

Clinical, echocardiographic and humoral status of patients following repair of tetralogy of Fallot: comparison of the second to the first decade.

Background: Surgical repair of tetralogy of Fallot may leave the patient with pulmonary regurgitation, causing eventual right ventricle dilatation and dysfunction. Predicting clinical deterioration may help to determine the best timing for intervention.

Objectives: To assess whether the clinical and humoral status of patients in the second decade after repair of ToF is worse than that of patients in the first decade after repair.

Analysis of segmental and global function of the fetal heart using novel automatic functional imaging.

Background: Functional assessment of the fetal heart has always been a challenge. Automatic functional imaging (AFI), a novel non-Doppler methodology based on 2-dimensional acoustic markers tracking, measures myocardial deformation regardless of angle of interrogation. Thus, we studied the validity of AFI in segmental and global assessment of myocardial function in the fetus.

N-terminal-proB-type natriuretic peptide as a marker for acute anthracycline cardiotoxicity in children.

Background: Anthracyclines are widely used in the treatment of pediatric cancer but their use is associated with cardiotoxicity. The cardiotoxic effect may become clinically apparent many years after therapy, and no reliable method exists for early detection of cardiac damage while the patient is receiving the drug. The natriuretic peptides have been established as markers for anthracycline-induced cardiotoxicity in adults and markers for cardiac dysfunction in children.

Assessment of fetal myocardial performance using myocardial deformation analysis.

Conventional techniques for the assessment of cardiac function on the basis of M-mode or 2-dimensional modalities are technically difficult, load dependent, and provide information on global ventricular function only. Newer techniques, which analyze myocardial performance, such as tissue velocity, strain, and especially the less load dependent strain rate, may provide more appropriate information. Myocardial systolic and diastolic motion and performance were calculated using tissue velocity, strain, and strain rate imaging on a large cohort of normal fetuses.

Comparison of N-terminal pro-B-type natriuretic peptide levels in critically ill children with sepsis versus acute left ventricular dysfunction.

Objective: N-terminal pro-B-type natriuretic peptide has been shown to be a marker for cardiac dysfunction. The peptide level is also elevated in patients with sepsis. The purpose of this study was to assess whether N-terminal pro-B-type natriuretic peptide levels can differentiate pediatric patients with sepsis from patients with acute left ventricular dysfunction.

N-terminal pro-B-type natriuretic peptide levels in acute versus chronic left ventricular dysfunction.

Objectives: To determine whether acute left ventricular dysfunction (LVD) causes significantly higher elevation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels than comparable chronic LVD.

Study Design: Plasma levels of NT-proBNP were measured in 10 pediatric patients diagnosed with acute LVD, in 7 pediatric patients with stable chronic dilated cardiomyopathy (DCM) and comparable levels of echocardiographic dysfunction, and during 5 episodes of acute exacerbation in patients with heart failure. Levels were compared using Mann-Whitney and analysis of variance for rank tests.

Symptomatic myocardial bridging in a child without hypertrophic cardiomyopathy.

Myocardial bridging (MB) is a rare coronary anomaly in children that is typically associated with hypertrophic cardiomyopathy or left ventricular hypertrophy. Several reports, mainly in adults, have suggested an association between MB and sudden death or ischemia without other cardiac abnormalities. In this report, we describe an 11-year-old girl with syncope and manifestations of cardiac ischemia associated with MB of the middle segment of the left anterior descending artery.

Repair of anomalous pulmonary artery with interposition graft: midterm results.

Anomalous pulmonary artery arising from the aorta is a rare congenital anomaly. The midterm results of repair of this malformation by Gore-Tex graft interposition were examined in 5 patients: 3 with anomalous right pulmonary artery and 2 with anomalous left pulmonary artery from the ascending aorta. Echocardiography was adequate in 4 cases for diagnosis, planning the operation, and follow-up.

Amino-terminal pro-brain-type natriuretic peptide: heart or lung disease in pediatric respiratory distress?

Objectives: The aim of this study was to determine whether plasma levels of amino-terminal pro-brain natriuretic peptide (N-BNP) could differentiate between heart failure and lung disease among infants with acute respiratory distress. In addition, our aim was to determine whether plasma levels of N-BNP could be used to monitor the effects of treatment among infants with heart failure.

Methods: Infants (age range: 1-36 months; median age: 10 months) who presented with respiratory distress underwent physical examination, plasma N-BNP measurement, and echocardiography within 24 hours after admission.

Tissue velocity Doppler assessment of atrial and ventricular electromechanical coupling and atrioventricular time intervals in normal subjects.

Mechanical events and electromechanical coupling are analyzed simultaneously in the atria and ventricles using tissue velocity imaging. Normal values for these parameters are provided.

Cardiovascular abnormalities associated with the Stuve-Wiedemann syndrome.

The Stuve-Wiedemann syndrome (SWS) is a congenital bone dysplasia characterized by camptodactyly with ulnar deviation and congenital bowing of the long bones. Affected patients present with respiratory difficulties in the neonatal period or later and recurrent episodes of hyperthermia. The typical radiological findings are bowing of the long bones of the lower limbs, wide metaphyses with decreased density, and abnormal trabecular pattern.

Absent ductus venosus in the fetus: review of the literature and first report of direct umbilical venous drainage to the coronary sinus.

The ductus venosus connects the portal and umbilical veins with the inferior vena cava and acts as a sphincter to protect the fetus from placental overcirculation. Its absence usually causes hydrops fetalis and is associated with high mortality rate, chromosomal anomalies and congenital malformations. In this condition, the umbilical vein almost always drains directly into right-sided structures such as inferior vena cava or right atrium.

Jagged1 gene mutation for abdominal coarctation of the aorta in Alagille syndrome.

Congenital cardiac defects such as peripheral pulmonary stenosis are well described in Alagille syndrome (AGS), which is transmitted in an autosomal dominant inheritance. Haploinsufficiency of the Jagged1 (JAG1) gene has been shown to cause AGS. Abdominal coarctation is an uncommon vascular congenital anomaly which has been described only three times in AGS.