Novel combination of FLNC (c.5707G>A; p. Glu1903Lys) and BAG3 (c.610G>A; p.Gly204Arg) genetic variant expressing restrictive cardiomyopathy phenotype in an adolescent girl.

Pediatric restrictive cardiomyopathy (RCM) is the rarest in its group and accounts for only 2.5-5% of all the diagnosed cardiomyopathies in children. It is a relentless disease with poor prognosis, and heart transplantation is the only long-term treatment option. The aetiology of pediatric RCM varies and includes conditions such as endomyocardial fibrosis, storage disorder (Fabry's disease, MPS), drugs, radiation, post-cardiac transplantation and genetic. Genetic causes encompasses mutations in sarcomeric (troponin I and T, actin, myosin and titin) and nonsarcomeric protein-coding genes (Desmin, RSK2, lamin A/C and bcl-2-associated athanogene 3 (BAG3)). Inheritance of RCM could be autosomal dominant, autosomal recessive and X-linked. Here, we report a case of RCM in an adolescent girl, who was symptomatic with palpitations and breathlessness on exertion. The patient showed presence of rare variants in FLNC (c.5707G>A; p.Glu1903Lys) and BAG3 genes (c.610G>A; p.Gly204Arg). These two variants were detected individually in asymptomatic father and mother, respectively. FLNC gene codes for gamma filamin. These filamin proteins play important role in maintaining the structural integrity of the sarcomere. BAG3 is the main component of the chaperone-assisted selective autophagy (CASA) pathway. Mutant FLNC leads to the formation of protein aggregates which are cleared by an active protein quality control system including CASA pathway. For further verification, in silico protein-protein interaction was performed using online software and tools. The results showed evident interaction between FLNC and BAG3 with significant binding score (-826.6) between them.

Partial Trisomy 16q21-q24.3 with Novel Cardiac Manifestation of Left Ventricular Noncompaction Cardiomyopathy: A Case Report.

Partial trisomy 16q is most often a consequence of malsegregation from a balanced parental translocation involving chromosome 16q. It is characterized by nonspecific craniofacial dysmorphic features, hypotonia, developmental delay, psychomotor retardation, and systemic manifestations of cardiac defect, renal abnormalities, and lung abnormalities. The survival of these patients depends upon the extent and severity of the organs involved. The present literature was replete with cases of partial trisomy 16q having structural cardiac defects. However, in the present report we described a novel finding of myocardial disease in the form of left ventricular noncompaction (LVNC) cardiomyopathy associated with this genetic condition.

The role of three-dimensional printed cardiac models in the management of complex congenital heart diseases.

BACKGROUND: Three-dimensional printing is a process enabling computer-assisted conversion of imaging data from patients into physical "printed" replicas. This has been extrapolated to reconstructing patient-specific cardiac models in congenital heart diseases. The aim of this study was to analyze the impact of three-dimensional printing in surgical decision making in selected cases of complex congenital heart disease by creating patient-specific printed models. METHODS: Patients with complex congenital heart diseases with unresolved management decisions after evaluation by echocardiography, cardiac catheterization, and cardiac computed tomography were included with intent to aid in surgical decision making. Three-dimensional models were created from computed tomographic images by an outsourced firm using computer applications. All cases were reviewed by the same team before and after the cardiac models were prepared. The management decisions were grouped as either "corrective surgery" or "no surgery or palliation" The impact of the surgical decision pre and post three-dimensional cardiac model was analyzed by applying Cohen's kappa test of agreement. RESULTS: Ten patients were included, of which five were of increased pulmonary blood flow, and five were of decreased pulmonary flow. The commonest indication for three-dimensional printed models was to establish the routability of the aorta and pulmonary artery to their respective ventricles (in five patients). The nonagreement between the decision taken before and after the cardiac model was 80%, with kappa -0.37 and P value 0.98. CONCLUSIONS: Three-dimensional printed cardiac models contribute to better decision making in complex congenital heart diseases enabling safer execution of any complex congenital heart surgery.

Isolated left ventricular apical hypoplasia in a young child.

A 16-month-old, healthy, asymptomatic male child presented with a diagnosis of dilated cardiomyopathy. Cardiovascular examination and chest radiograph were normal. ECG revealed sinus rhythm, and the augmented vector left lead showed raised ST segment, T wave inversion and q waves. Echocardiography showed a globular left ventricle with notched cardiac apex, abnormal echogenicity in the left ventricular apical myocardium, single papillary muscle and normal biventricular function. Cardiac MRI scan revealed a globular left ventricle with fibrofatty changes and retraction of the apex, the papillary muscles closely approximated, and the right ventricle wrapping around the apex of the left ventricle. This is described as isolated left ventricular apical hypoplasia. Diagnosis of this rare entity can be made by MRI, and it has been diagnosed largely in adults. The pathophysiology and long-term outcomes are unknown. We characterise the echocardiography findings of this rare anomaly in a child for the first time in the literature.

An evolving anesthetic protocol fosters fast tracking in pediatric cardiac surgery: A comparison of two anesthetic techniques.

BACKGROUND: The past two decades have seen rapid development of new surgical techniques for repair as well as palliation of complex congenital heart diseases. For a better patient outcome, minimal postoperative ventilation remains one of the most important endpoints of an effectual perioperative management. AIMS AND OBJECTIVES: The aim of this randomized open-label trial was to compare postoperative extubation time and intensive care unit (ICU) stay when two different anesthetic regimens, comprising of induction with ketamine and low-dose fentanyl versus high-dose fentanyl, are used, in pediatric patients undergoing corrective/palliative surgery. MATERIALS AND METHODS: Patients with congenital cardiac defects, under 14 years of age undergoing cardiac surgery under cardiopulmonary bypass (CPB) and epidural analgesia, were enrolled into two groups - Group K (ketamine with low-dose fentanyl) and Group F (high-dose fentanyl) - over a period of 10 months, starting from January 2018. The effect of both these drugs on postoperative extubation time and ICU stay was compared using Mann-Whitney U-test. RESULTS: A total of 70 patients were assessed with equal distribution in both the groups. In Group K, 32 of 35 patients were extubated in the operation room, whereas extubation time in Group F was18.1 ± 11 h. Total ICU stay in Group K and Group F was 45.2 ± 30.1 and 60.1 ± 24.5 h, respectively (P = 0.02). Systolic blood pressure was significantly higher in Group K. CONCLUSION: Ketamine along with low-dose fentanyl, when used for anesthetic induction, in comparison to high-dose fentanyl, reduces postoperative extubation time and ICU stay, in pediatric patients undergoing corrective/palliative surgery under CPB and epidural analgesia for congenital cardiac defects.

Bed wetting - silent suffering: an approach to enuresis and voiding disorders in children.

Bed wetting or nocturnal enuresis is a common problem among children. It is either monosymptomatic or may be associated with a voiding disorder. Many factors may contribute towards enuresis such as developmental delay, heredity, inappropriate nocturnal anti diuretic hormone secretion and reduced bladder capacity. Any child presenting with bed-wetting should be evaluated for any underlying bladder dysfunction before labeling as monosymptomatic enuresis. The evaluation consists of structured bowel and bladder history, detailed clinical examination, frequency volume record and appropriate investigations. The frequency volume diary is an indispensible component of evaluation and helps in establishing diagnosis and tailoring therapy. The treatment of monosymptomatic enuresis consists of positive psychological support, alarms and medication (desmopressin/ anticholinergics/ imiprammine). Children with features of underlying bladder dysfunction, anatomical anomalies and neurological disorders should be referred to a pediatrician without delay. The outcome of therapy is usually rewarding but varies, depending on the underlying etiology, motivation, compliance and family support. The cure rates with alarms are better than with desmopressin in monosymptomatic enuresis. Timely and appropriate therapy yields better outcomes. Thus, a thorough, scientific and evidence based approach is essential in children presenting with bed-wetting.

Non invasive urodynamic assessment in children--are they reliable? Validation of non-invasive urodynamics in children with functional voiding disorders.

OBJECTIVES: To validate the non-invasive tests that can predict the type of bladder dysfunction normally diagnosed by invasive urodynamics. METHODS: Children below 12 yrs of age were evaluated prospectively. Non-invasive urodynamic evaluation included history, clinical examination, frequency volume charting, ultrasonographic scan, urine analysis and renal function tests. Micturating cystourethrogram was carried out in children with recurrent urinary tract infections. All children underwent invasive urodynamic studies and the significance of association of the parameters of noninvasive assessment with invasive urodynamics was determined. Chi square test using Epi 6 software was used for statistical analysis of data. RESULTS: 41 children underwent invasive urodynamic studies. The commonest disorder was detrusor instability in 28 (68.2%). Dysynergic voiding was noted in 8 (19.5%). The study was normal in 5 (12.1%). Nocturnal enuresis with day time symptoms, holding maneuvers, small frequent voiding pattern (p<0.05) and a small capacity bladder with insignificant residue (p=0.0003) predicts detrusor instability. Straining (p=0.0006), large capacity bladder with significant post void residue in the absence of vesicouretric reflux (p<0.05) predicts dysyneric voiding. On combining the various non-invasive tests and validating them against invasive urodynamics in diagnosing detrusor instability and dysnergic voiding, they have a sensitivity of 88.4% and 87.5%, specificity of 72.7% and 69.2%, positive predictive value of 0.88 and 0.63 and positive likelihood ratio of 3.1 & 2.2 respectively. CONCLUSIONS: Functional voiding disorders can be diagnosed with reasonable accuracy by minimally invasive methods.

Recurrent urinary tract infection and functional voiding disorders.

This study was carried out to determine the association of recurrent urinary tract infections with functional voiding disorders. Sixty eight children with suspected functional voiding disorders were prospectively evaluated clinically and by non-invasive urodynamics. Invasive urodynamics were carried out when indicated. Group I comprised 34 children with symptoms suggestive of functional voiding disorders and recurrent urinary tract infections (mean age 6.3+/-2 yr) and Group II comprised 34 children with symptoms suggestive of functional voiding disorders without recurrent urinary tract infections (mean age 6.7+/-2 yr). The underlying bladder abnormalities in Groups I and II were detrusor instability in 22 (64.7%) and 30 (88.2%), respectively (P>0.05) and dysynergic voiding in 10 (29.4%), and 1 (2.9%), respectively (P<0.05). Children with recurrent urinary tract infections are more likely to have a dysynergic voiding pattern than children presenting with other symptoms of functional voiding disorders.