Left Ventricular Non-compaction: Is It Genetic?

Left ventricular non-compaction (LVNC) is reported to affect 0.14 % of the pediatric population. The etiology is heterogeneous and includes a wide number of genetic causes. As an illustration, we report two patients with LVNC who were diagnosed with a genetic syndrome. We then review the literature and suggest a diagnostic algorithm to evaluate individuals with LVNC. Case 1 is a 15-month-old girl who presented with hypotonia, global developmental delay, congenital heart defect (including LVNC) and facial dysmorphism. Case 2 is a 7-month-old girl with hypotonia, seizures, laryngomalacia and LVNC. We performed chromosomal microarray for both our patients and detected chromosome 1p36 microdeletion. We reviewed the literature for other genetic causes of LVNC and formulated a diagnostic algorithm, which includes assessment for syndromic disorders, inborn error of metabolism, copy number variants and non-syndromic monogenic disorder associated with LVNC. LVNC is a relatively newly recognized entity, with heterogeneity in underlying etiology. For a systematic approach of evaluating the underlying cause to improve clinical care of these patients, a diagnostic algorithm for genetic evaluation of patients with LVNC is proposed.

Loeys-Dietz syndrome in a Southeast Asian Hospital: a case series.

UNLABELLED: Loeys-Dietz syndrome (LDS) is a heritable connective tissue disease in which the activity of the transforming growth factor (TGF) beta signalling pathway is disrupted. The clinical features of LDS represent a clinical continuum that includes LDS type 1, with cutaneous, vascular, skeletal and craniofacial findings, and LDS type 2, with cutaneous, vascular and skeletal findings. We describe five Asian patients with genetically confirmed LDS with mutations in either the TGFBR1 or TGFBR2 gene. Their clinical features were similar to those reported in Caucasian patients. Two patients have novel mutations in TGFBR2. Transcatheter occlusion of patent ductus arteriosus (PDA) was safe and successful in three patients. Treatment with Losartan for aortic root dilatation was well tolerated in our patients, but the outcome is mixed. Among the three patients with follow-up data, aortic root dilatation has improved in two patients but continues to progress in the third patient despite treatment. CONCLUSION: We describe two novel mutations in TGFBR2 leading to LDS; PDA is common in our patients and can be safely occluded via transcatheter procedure.

Case report: the 'vanished' left pulmonary artery.

Background: We report a case of isolated ductal origin of pulmonary artery (DOPA) diagnosed in an asymptomatic newborn. The primary aim of this case is to highlight the need to investigate for DOPA in patients diagnosed with an 'absent branch pulmonary artery'. Case summary: Our patient was an asymptomatic newborn infant, with normal intracardiac anatomy. He was initially diagnosed post-natally with 'absent left pulmonary artery' (LPA), though the LPA was seen in antenatal scans. He underwent angiography and was re-diagnosed with bilateral arterial ducts, with ductal origin of the LPA from the left arterial duct. The LPA was salvaged by first stenting the left arterial duct on Day 11 of life, with subsequent surgery to connect the LPA to the main pulmonary artery at 4.5 months old. The patient had an uneventful recovery after the surgery. Discussion: Ductal origin of pulmonary artery is a rare vascular anomaly characterized by continuity of the left or right pulmonary artery (PA) with the distal end of the arterial duct, and discontinuity with the main PA. It is commonly misdiagnosed as pulmonary artery agenesis when the patent arterial duct constricts, with cessation of blood flow into the affected pulmonary artery. A high index of suspicion is necessary for diagnosis of DOPA. Once diagnosed, this lesion is clearly amenable to intervention, with benefits from unifocalization, to prevent late onset pulmonary hypertension or cardiac failure.

Endocardial Fibroelastosis as an Independent Predictor of Atrioventricular Valve Rupture in Maternal Autoimmune Antibody Exposed Fetus: A Systematic Review with Clinicopathologic Analysis.

BACKGROUND: Neonatal lupus (NL) is a clinical syndrome that develops in the fetus as a result of maternal autoimmune antibodies. Congenital complete heart block (CHB) is the most common manifestation, while extranodal cardiac manifestations of NL, such as endocardial fibroelastosis (EFE) and myocarditis, are rare but more serious. Less is known about this atrioventricular valve rupture due to valvulitis as a consequence of maternal autoantibodies. We have described a case of cardiac neonatal lupus with an antenatally detected CHB patient who developed mitral and tricuspid valve chordal rupture at 45 days of age. We compared the cardiac histopathology and the fetal cardiac echocardiographic findings of this case with another fetus that was aborted after being antenatally diagnosed with CHB but without valvar rupture. A narrative analysis after a systematic review of the literature regarding atrioventricular valve apparatus rupture due to autoimmune etiology along with maternal characteristics, presentation, treatment, and outcome have been discussed in this article. OBJECTIVES: To describe published data on atrioventricular valve rupture in neonatal lupus, including clinical presentation, diagnostic evaluation, management, and outcomes. METHODS: We conducted a PRISMA-compliant descriptive systematic examination of case reports that included accounts of lupus during pregnancy or in the newborn period that resulted in an atrioventricular valve rupture. We gathered information on the patient's demographics, the details of the valve rupture and other comorbidities, the maternal therapy, the clinical course, and the results. We also used a standardized method to evaluate the cases' quality. A total of 12 cases were investigated, with 11 cases drawn from 10 case reports or case series and 1 from our own experience. RESULTS: Tricuspid valve rupture (50%) is more common than mitral valve rupture (17%). Unlike mitral valve rupture, which occurs postnatally, the timing of tricuspid valve rupture is perinatal. A total of 33% of the patients had concomitant complete heart block, while 75% of the patients had endocardial fibroelastosis on an antenatal ultrasound. Antenatal changes pertaining to endocardial fibroelastosis can be seen as early as 19 weeks of gestation. Patients with both valve ruptures generally have a poor prognosis, especially if they occur at close intervals. CONCLUSION: Atrioventricular valve rupture in neonatal lupus is rare. A majority of patients with valve rupture had antenatally detected endocardial fibroelastosis in the valvar apparatus. Appropriate and expedited surgical repair of ruptured atrioventricular valves is feasible and has a low mortality risk. Rupture of both atrioventricular valves occurring at close intervals carries a high mortality risk.

Chest pain attendances to a Paediatric Emergency Department pre- and post-COVID-19 vaccination.

Background: Introduction of the mRNA vaccination for coronavirus disease 2019 (COVID-19) has been associated with an increase in cases of peri/myocarditis. In our retrospective cross-sectional study, we aim to (I) describe paediatric chest pain attendance, and (II) study resource utilisation in the Emergency Department (ED) of KK Women's and Children's Hospital (KKH), stratified by pre-pandemic, during the pandemic pre- and post-COVID vaccination introduction in adolescents. Methods: We reviewed records of adolescents aged 12 to 18 years old who presented to our ED with the triage complaint of chest pain between 1 January 2019 to 31 January 2022, and determined the attendance rates, aetiologies and resource utilisation during the above time periods. Results: There were 2,418 ED attendances for chest pain in our study population. Among 887 inpatient admissions for chest pain, 1.8% were attributed to a cardiac cause. Comparing the pre-pandemic period to the period after the mRNA COVID-19 vaccination was introduced, ED chest pain rates increased from a median of 0.5% of ED attendances [interquartile range (IQR), 0.3-0.5%] to 0.9% (IQR, 0.7-2.0%) (P<0.001), while admission rates increased from a median of 26.2% of ED attendances (IQR, 24.1-29.1%) to 40.9% (IQR, 37.6-56.6%) (P<0.001). Cardiac enzyme orders among ED visits for chest pain increased from a pre-pandemic median of 0% (IQR, 0.0-2.6%) to a post-vaccination median of 26.1% (IQR, 17.2-56.2%) (P<0.001) and were due to concerns for vaccine-related myocarditis. Seven cases of probable vaccine-related myocarditis presented with chest pain to our ED. Conclusions: Paediatric chest pain is largely non-cardiac in origin. ED chest pain attendance rates and resource utilisation increased after the introduction of mRNA COVID-19 vaccination in adolescents.

Multisystem inflammatory syndrome in children in Singapore.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome with multisystem involvement affecting children exposed to COVID-19. This condition is rarely reported in East Asia and was not detected in Singapore until 2021. We present 12 cases of MIS-C diagnosed in KK Women's and Children's Hospital (KKH) from October 2021 to December 2021. METHOD: We conducted an observational study on cases fulfilling the Singapore Ministry of Health criteria for MIS-C from January 2020 to December 2021 in KKH. Medical records were reviewed to obtain information on clinical presentation, disease course, treatment received and outcomes. RESULTS: In the 12 cases detected, the median age was 7.50 years (interquartile range 4.00-9.25); 8 were male. All patients had mucocutaneous symptoms similar to Kawasaki disease. Other commonly involved systems were: haematological (coagulopathy 100%, lymphopaenia 91.70% and thrombocytopaenia 75.00%), gastrointestinal (75.00%) and cardiovascular (83.30%). Six patients (50.00%) had shock and were admitted to the intensive care unit. The majority of patients received treatment within 2 days of hospitalisation with intravenous immunoglobulin (IVIg) and steroids. All survived; the majority had normal echocardiograms and no long-term organ sequelae at 6 months post-discharge. CONCLUSION: MIS-C emerged in Singapore as the incidence of COVID-19 in the community increased in 2021. The clinical presentation of our patients is similar to earlier reports, with some significant differences from Kawasaki disease. Multidisciplinary management, timely diagnosis, and early initiation of treatment with IVIg and steroids likely contributed to comparatively good outcomes. Our cases highlight the need for continued awareness of MIS-C among physicians, and surveillance of its incidence, short- and long-term outcomes.

Saline contrast echocardiography complements cardiac interventions in neonates with transposition of great arteries and abnormal ductus venosus anatomy.

We present a rare case of premature low birthweight neonate with right diaphragmatic hernia and transposition of great vessels requiring balloon atrial septostomy. Congenital diaphragmatic hernia poses a unique challenge to umbilical venous catheterisation. Based on the radiographic position of umbilical vein catheter, umbilical venous cannulation was attempted; however, the catheter could not be navigated to the right atrium. Saline contrast echocardiography was used to delineate the abnormal umbilical and ductus venosus drainage. Eventually, the procedure was successfully completed via the femoral venous approach. We emphasise the importance of defining ductus venosus anatomy and umbilical venous drainage using a simple tool like saline contrast echocardiography before performing catheterisation using the umbilical venous access in such cases.

Persistent hypercholesterolemia in child with homozygous autosomal recessive hypercholesterolemia: A decade of lipid management.

Autosomal recessive hypercholesterolemia (ARH) is a rare form of genetic hypercholesterolemia caused by mutations in low density lipoprotein receptor adaptor protein 1 (LDLRAP1). The proband first presented with linear eruptive xanthomas over her ankles, knees and elbows, with low density lipoprotein cholesterol (LDL-C) of 16.0 mmol/L (618.7 mg/dL), at 2.5 years old. Next generation sequencing revealed a novel homozygous mutation in LDLRAP1 exon 5 (c.466delG). In the first year, drug regimens of either cholestyramine or simvastatin, reduced her LDL-C to 10.5 mmol/L (406 mg/dL) and 11.7 mmol/L (452.4 mg/dL), respectively. Combination simvastatin and ezetimibe was the mainstay of therapy from age 5 - 10 years. Her lowest achieved LDL-C was 6.3 mmol/L (243.6 mg/dL). Switching to atorvastatin did not lead to further reduction. Carotid intima-media thickness was 0.47 mm (> 97th percentile) and 0.32 mm (75 - 95th percentile) at ages 8 years and 11 years, respectively. Addition of monthly injections of evolocumab for 3 months, led to an increase in LDL-C, from 7.0 mmol/L (270.7 mg/dL) to a range of [(8.4 - 9.1) mmol/L or (324.8 - 351.9) mg/dL]. In this report, a decade-long lipid management is described in a patient with ARH. Residual activity of LDLRAP1 is a likely determinant of her response. Clinical management remains sub-optimal and options for the paediatric population are limited. Novel classes of cholesterol-lowering medications are needed for this ultra-rare and severe hypercholesterolemia.

Screening for congenital heart disease in a Singapore neonatal unit.

INTRODUCTION: Congenital heart disease (CHD) is a leading cause of infant mortality. The aim of this study was to evaluate the efficacy of a neonatal screening programme for CHD before the introduction of pulse oximetry. METHODS: This was a retrospective review of live births in the period 2003-2012. Cases of CHD were detected through prenatal ultrasonography and/or postnatal examination, and confirmed using two-dimensional echocardiography. Data was rigorously checked against multiple sources. The antenatal detection rate, sensitivity, specificity, predictive values and likelihood ratios of the screening programme were analysed for all cases of CHD and critical CHD. RESULTS: The incidence of CHD was 9.7 per 1,000 live births. The commonest CHD was ventricular septal defect (54.8%). The antenatal detection rate was three times higher in the critical CHD group (64.0%) compared to the group as a whole (21.1%). The sensitivity and specificity of screening was 64.5% and 99.7% for all CHD, and 92.9% and 99.1% for the critical CHD group, respectively. The positive likelihood ratio was 215 and 103, while the negative likelihood ratio was 0.36 and 0.07 for all CHD and critical CHD, respectively. CONCLUSION: The CHD screening programme had excellent specificity but limited sensitivity. The high positive likelihood ratios indicate that where sufficient risk factors for CHD are present, a positive result effectively confirms the presence of CHD. The low negative likelihood ratio for critical CHD indicates that, where prior suspicion for critical CHD is low, a negative result is reassuring.

Reperfusion Injury with Compartment Syndrome Following Systemic Thrombolysis for Cardiac Catheterization-Related Arterial Thrombosis in an Infant.

Systemic thrombolysis is increasingly used for management of arterial thrombosis following cardiac catheterization, and complications apart from bleeding manifestations are not well reported. We report the case of an infant with lower limb ischemia secondary to femoral arterial thrombosis, which developed after cardiac catheterization. Systemic thrombolysis resulted in successful reperfusion of the lower limb. However, the infant subsequently developed compartment syndrome, requiring an emergent fasciotomy. This case highlights the importance of surveillance for the development of reperfusion injury-related compartment syndrome postsystemic thrombolysis for arterial thrombosis.

Mismatch between poor fetal growth and rapid postnatal weight gain in the first 2 years of life is associated with higher blood pressure and insulin resistance without increased adiposity in childhood: the GUSTO cohort study.

BACKGROUND: Using longitudinal ultrasounds as an improved fetal growth marker, we aimed to investigate if fetal growth deceleration followed by rapid postnatal weight gain is associated with childhood cardiometabolic risk biomarkers in a contemporary well-nourished population. METHODS: We defined fetal growth deceleration (FGD) as ultrasound-measured 2nd-3rd-trimester abdominal circumference decrease by ≥0.67 standard deviation score (SDS) and rapid postnatal weight gain (RPWG) as 0-2-year-old weight increase by ≥0.67 SDS. In the GUSTO mother-offspring cohort, we grouped 797 children into four groups of FGD-only (14.2%), RPWG-only (23.3%), both (mismatch, 10.7%) or neither (reference, 51.8%). Adjusting for confounders and comparing with the reference group, we tested associations of these growth groups with childhood cardiometabolic biomarkers: magnetic resonance imaging (MRI)-measured abdominal fat (n = 262), liver fat (n = 216), intramyocellular lipids (n = 227), quantitative magnetic resonance-measured overall body fat % (BF%) (n = 310), homeostasis model assessment of insulin resistance (HOMA-IR) (n = 323), arterial wall thickness (n = 422) and stiffness (n = 443), and blood pressure trajectories (ages 3-6 years). RESULTS: Mean±SD birthweights were: FGD-only (3.11 ± 0.38 kg), RPWG-only (3.03 ± 0.37 kg), mismatch (2.87 ± 0.31 kg), reference (3.30 ± 0.36 kg). FGD-only children had elevated blood pressure trajectories without correspondingly increased BF%. RPWG-only children had altered body fat partitioning, higher BF% [BF = 4.26%, 95% confidence interval (CI) (2.34, 6.19)], HOMA-IR 0.28 units (0.11, 0.45)] and elevated blood pressure trajectories. Mismatch children did not have increased adiposity, but had elevated ectopic fat, elevated HOMA-IR [0.29 units (0.04,0.55)] and the highest blood pressure trajectories. Associations remained even after excluding small-for-gestational-age infants from analyses. CONCLUSIONS: Fetal growth deceleration coupled with rapid postnatal weight gain was associated with elevated childhood cardiometabolic risk biomarkers without correspondingly increased BF%.