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Amyotrophic lateral sclerosis (ALS) is a rare disorder that affects both upper and lower motor neurons. Mutations in Alsin Rho Guanine Nucleotide Exchange Factor (ALS2) correlates with three similar but distinctive syndromes, including the juvenile form of ALS. An Iranian Kurdish family was involved in this study and all members were evaluated with relevant clinical guidelines. Whole exome sequencing and sanger sequencing were applied to all family members to undermine the possible genetic factors. A substitution c. 2110 CT (p. Arg704X) identified in the

Introduction: The people worldwide have been affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection since its appearance in December, 2019. Kawasaki disease-like hyperinflammatory shock associated with SARS-CoV-2 infection in previously healthy children has been reported in the literature, which is now referred to as a multisystem inflammatory syndrome in children (MIS-C). Some aspects of MIS-C are similar to those of Kawasaki disease, toxic shock syndrome, secondary hemophagocytic syndrome, and macrophage activation syndrome. Case Presentation: This study reported an 11-year-old boy with MIS-C presented with periorbital and peripheral edema, abdominal pain, elevated liver enzymes, severe right pleural effusion, moderate ascites, and severe failure of right and left ventricles. Conclusions: Due to the increasing number of reported cases of critically ill patients afflicted with MIS-C and its life-threatening complications, it was recommended that further studies should be carried out in order to provide screening tests for myocardial dysfunction. Adopting a multidisciplinary approach was found inevitable.

Mulibrey Nanism is a rare multisystem disorder inherited in an autosomal recessive manner caused by mutations in the TRIM37 gene. Most of the reported cases are from Finland, but this condition has rarely occurred in other countries. Although the clinical diagnosis of Mulibrey nanism is a challenge during the first months of life, the disease can be suspected clinically due to the distinctive features of the patients. A 4-year-old female with pneumonia, cardiomyopathy, growth retardation, peripheral edema, and characteristic craniofacial features was referred to Tehran Hope Generation Foundation Genetic diagnosis Center, in October 2021. Genomic DNA was isolated from peripheral blood samples of the patient and her parents and Whole exome sequencing was performed for the patient. Whole exome sequencing revealed a homozygous G>A splice site variant (TRIM37; c.370-1G>A). Sanger sequencing confirmed the segregation of the variant with phenotype in this family. Whole exome sequencing can be helpful in the diagnosis of the patients suspecting to Mulibrey nanism and lacking sufficient clinical presentation according to the diagnostic algorithm.

Kawasaki disease (KD) is often complicated by coronary artery lesion (CAL), including dilatation or aneurysms. Intravenous immunoglobulin (IVIG) is used with aspirin to prevent CAL in KD.Given that the primary treatment for other vasculitis is the use of corticosteroids, this study has been performed to evaluate the effect of intravenous methylprednisolone pulse (IVMP) therapy in preventing CAL in KD.A randomized, single-blind clinical trial was conducted on 40 KD patients aged six months to five years. Patients were randomized into two groups according to the main treatment plan in addition to aspirin: case group (IVMP for three consecutive days and then oral prednisolone for three days) and control group (intravenous immunoglobulin 2 g/kg). Echocardiography was performed for all children at least three times, during the acute phase, two weeks, and two months later.Data analysis at the end of the study was done on 40 patients (20 patients in each group). There were no significant differences in age and sex distribution, mean fever, and acute phase duration, as well as baseline echocardiography in the two groups. The frequency of CAL was 20% in the case group and 45% in the control group, after two weeks (p0.05), but there was no significant difference between two groups in types of coronary artery lesion after two weeks and the frequency and severity of CAL after two months.IVMP as initial line therapy effectively control systemic and vascular inflammation and decrease coronary artery damage in KD.

Primary congenital glaucoma (PCG) (OMIM#231,300) can be caused by pathogenic sequence variations in CYP1B1, LTBP2, MYOC and PXDN genes. The purpose of this study was to investigate mutations in the CYP1B1 gene in families affected with primary congenital glaucoma (PCG) using linkage analysis and Sanger sequencing. A total number of four families with nine affected PCG patients during six months were included in this study. The mutations were identified by homozygosity mapping to find the linked loci and then direct sequencing of all coding exons, the exon–intron boundaries and the 5' untranslated region of CYP1B1 using genomic DNA obtained from affected family members and their parents. Moreover, bioinformatic tools were applied to study mutation effect on protein structure and function. A total of four mutations were identified, and three of these were novel. Two were missense mutations: One was truncating mutation, and the other was an in-frame deletion. Mutations in CYP1B1 could fully explain the PCG phenotype in all of the patients. Also, the bioinformatic study of the mutations showed the structure of the protein is affected, and it is well conserved among similar species. In this study, we identified 4 CYP1B1 mutations, 3 of which were novel. In silico analysis of identified mutations confirmed their molecular pathogenicity. A similar analysis will help understand the biological role of CYP1B1 and the effect of mutations on the regulatory and enzymatic functions of CYP1B1 that result in PCG. Not relevant

Background and Aims: Congenital heart defects (CHD) are the most common type of congenital disability. Copy number variations (CNVs) have been found as one of the genetic etiology of non-syndromic CHD, and researchers have detected several pathogenic CNVs in patients with cardiac defects. Materials and Methods: In the present study, 70 patients with familial (20 patients) and sporadic (50 patients) non-syndromic CHD were evaluated to find whether CNVs in the GATA4, NKX2-5, TBX-5, CREL, BMP4 genes, and 22q11.2 region contribute to the pathogenesis of non-syndromic CHD. We have used the Multiplex Ligation-dependent Probe Amplification (MLPA) technique as a molecular method to identify CNVs in predefined loci. Results: Normal MLPA results were demonstrated for GATA4, NKX2-5, TBX-5, CRELD, and BMP4 genes for all sporadic and familial cases. However, we found three patients with imbalances for the 22q11.2 region. One patient with 22q11.2 deletion showed tetralogy of fallot, and the other had ventricular septal defects/ pulmonary atresia/ multiple aortopulmonary collateral arteries. A duplication of the 22q11.2 region was detected in one patient with patent ductus arteriosus. Conclusion: Identifying genomic imbalances in 6% of the non-syndromic sporadic patients indicates that recurrent CNVs could be associated with non-syndromic CHD. It seems that it is the first CNV analysis using MLPA carried out in Iranian patients with cardiac defects. We suggest that 22q11.2 imbalances should be considered in patients with cardiac lesions to provide an accurate diagnosis and appropriate genetic counseling in affected families.

Tricuspid annular plane (TAP) systolic excursion (TAPSE) is a reproducible M-mode parameter for the measurement of longitudinal shortening of the right ventricle (RV). To date, all attention has been focused on the systolic excursion of TAP and the diastolic excursion of the annular plane back to the base has been ignored. This study aims to compare the quantitative (excursion, slope, and duration) and qualitative (velocity, acceleration, and indentation) characteristics of TAP systolic and diastolic excursion, using color tissue Doppler imaging, in three groups of children with normal RV (NORV), volume overloaded RV (VORV), and pressure overloaded RV (PORV) and normal pulmonary arterial pressure.A prospective case-control study was performed in three groups of children with normal heart, VORV and PORV. TAPSE and tricuspid annular plane diastolic excursion (TAPDE) were quantitatively and qualitatively analyzed and compared between the three groups. Statistical analysis was performed using IBM SPSS Statistics for Windows.TAPSE, TAPDE, TAPSE slope, TAPSE slope/TAPDE slope, TAPDE duration and TAPDE duration/RR interval were lower in PORV (TAPSE: PORV: 14.45 ± 4.30, NORV: 20.45 ± 5.46, P = .003, TAPDE:PORV: 14.39 ± 4.61, NORV: 20.28 ± 5.65, P = .004, TAPSE slope:PORV: 4.79 ± 1.40, NORV: 7.15 ± 1.98, P = .001, .001, TAPDE duration:PORV: 201.1 ± 87.9 ms, NORV: 292.1 ± 97.9, P = .006, TAPDE duration/RR interval: PORV: .37 ± .09, NORV: .48 ± .08, P = .0002).Pressure-overload on RV produced more impairment of TAPSE and TAPDE patterns than volume overload. Values of TAPSE and TAPDE in patients with VORV and PORV stay in two ends of the normal spectrum. The harmful impact of pre-tricuspid volume overload seems to be less than the post-tricuspid volume overload.

Pulmonary artery‐focused agitated saline contrast echocardiography unveils tricky cases of ALCAPA by the entry of microbubbles into the left coronary artery (LCA) during systole and retrograde flow from LCA into the main pulmonary artery during diastole. Associated pulmonary hypertension, if present, augments the former flow and supplemental oxygen increases the latter.

BackgroundKawasaki disease (KD) is often complicated by coronary artery damage, including dilatation or aneurysms. IVIG is used with aspirin to prevent coronary artery abnormalities in KD. Since the primary treatment for other vasculitis is the use of corticosteroids, this study has been performed to evaluate the effect of intravenous pulse methylprednisolone therapy in preventing coronary artery lesions in KD.MethodA randomized, single-blind clinical trial was conducted on 40 KD patients aged 6 months to 5 years. Patients were randomized into two groups according to the main treatment plan in addition to aspirin: case group (intravenous methylprednisolone pulse for three consecutive days and then oral prednisolone for 5 days) and control group (intravenous immunoglobulin 2 gram/kg). Echocardiography was performed for all children at least 3 times, during the acute phase, two weeks, and two months later.ResultsData analysis at the end of the study was done on 40 patients (20 patients in each group). There were no significant differences in age and sex distribution, mean fever, and acute phase duration, as well as baseline echocardiography in 2 groups. The frequency of coronary artery lesion was 20% in the case group and 45% in the control group, after two weeks (pConclusionIntravenous methylprednisolone pulse as initial line therapy effectively control systemic and vascular inflammation and decrease coronary artery damage in KD.

Objectives: This study compared the success rate of atrial septal defect device closure in children with and without balloon sizing during the procedure. Methods: This four-year, combined retrospective and prospective study was performed at a single center. All participants underwent transcatheter closure under transthoracic echocardiography and the success rate was analyzed considering the effect of balloon sizing. Results: Eighty-eight patients with a mean age of 6.48 ± 3.32 years were enrolled. Balloon sizing was performedor in 39 (44%) patients. It didn’t change the success rate compared to 49 (56%) patients without balloon sizing. Likewise, age and sex had no effect on thesuccess rate. However; the failure rate was higher in patients with larger defects. Conclusions: The study demonstrated that balloon sizing did not influence the success rate of atrial septal defect device closure, and a precise measurement by echocardiography can be as successful as balloon sizing.

Background: Congenital heart disease (CHD) is the most common congenital disorder in neonates. Many factors are associated with the occurrence of the CHD, including genetic factors, teratogenic exposure and several other unrecognized factors. Objectives: This study aims to investigate the role of several potential factors associated with the occurrence of CHD. Methods: This study was conducted as a cross-sectional case-control study, in Imam Khomeini Hospital Complex, Tehran, Iran. A total of 1338 known cases of CHD, diagnosed by echocardiography or angiography and 1201 healthy children as the controls were included in this study. Factors that could have an association with CHD were investigated by a questionnaire from all participants. Results: Maternal age above 30 years (P-value < 0.001), positive parents’ consanguinity (P-value < 0.001) and previous maternal history of abortion (P-value < 0.001) was significantly higher among patients with CHD; furthermore, positive history of CHD among siblings of the known cases of CHD was higher than healthy ones (P-value < 0.001). The mean birth weight in case and control group were 3 (+ 0.648) and 2.9 (+ 0.707) kilograms, respectively. The maternal age in 983 (73.4%) cases and 960 (79.93%) controls was below the 30 years, the maternal age for other participants was above the 30 years (P-value < 0.001). Conclusions: All factors except the history of stillbirth, maternal underlying disease and drug use during pregnancy in the case group were significantly different with the control group. It seems that the causes of CHD in Iran are most commonly related to the hereditary genetic factors, and the increased maternal age, drug use, and underlying diseases in the mother are a matter of less importance.

Introduction Schizophrenia is recognized as one of the most important mental illnesses of the last century. Many genetic and environmental factors are involved in this condition. Recently, the genome-wide association study identified two significant genes LRP8 and CEP85L associated with psychiatric disorders. LRP8 (low-density lipoprotein receptor-related protein 8) acts as a cytoplasmic receptor for Reelin. Many studies have revealed that LRP8 was significantly related to schizophrenia and bipolar disorder in Chinese population. CEP85L standing for 'centrosomal protein 85 kDa-like' is another gene, which has been reportedly associated with BPD. Methods We performed a case-control study to analyze the association between rs5177 single-nucleotide polymorphism in the LRP8 gene plus the single-nucleotide polymorphism rs11756438 in the CEP85L gene and schizophrenia in the Iranian population. The genotype for rs5177 was determined by ARMS PCR method, while for rs11756438 genotype, it was determined by PCR-RFLP method after which statistical analysis was performed for each polymorphism. In rs5177, the CC genotype was susceptible to the disease while G allele was associated with disease protection. Results and Conclusion In rs11756438, the AA genotype was associated with disease susceptibility, while allele A did not have a significant association with the disease.

COVID-19 as a viral infection is usually asymptomatic in children, but complication of this disease in children is not rare and may be fatal Hyper inflammation of COVID-19 is a potential fatal in undiagnosed children It is very similar to Kawasaki disease but with higher mortality and morbidity Multisystem inflammatory syndrome in children (MIS-C) and multi-organ involvement was reported in hyper inflammation syndrome following COVID19 Herein we report our algorithmic approach to Kawasaki-like syndromes due to COVID-19 in our center Based-on this approach we had no mortality during the last 5 months [ABSTRACT FROM AUTHOR] Copyright of Iranian Journal of Pediatrics is the property of Kowsar Corporation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )

Interferon-β (IFN-β) is among the first drugs used for reducing the symptoms of multiple sclerosis (MS). Many studies show that the genetic predisposition of patients might modulate their response to IFN-β treatment. In this study GAPVD1 gene expression and the genotyping of rs2291858 variant were analysed in 100 responder and 100 non-responder patients with MS treated using IFN-β. Moreover, rs2291858 genotyping was performed for 200 patients with MS and 200 healthy controls. GAPVD1 expression was significantly increased in the responder patients than in non-responders and the distribution of rs2291858 polymorphism was significantly different between them. The GAPVD1 expression level in AA genotype of the responder group was higher than that in other genotypes of these two groups. The results show that the GAPVD1 expression level and rs2291858 genotype probably affect the response to IFN- β in patients with MS.

Background: The arterial switch operation [ASO] is the surgical procedure of choice for correction of the TGA. This is one of the most complex cardiac surgeries, with coronary artery transfer being the most important factor determining the success of the surgery. Objectives: This study aims to investigate the outcomes of ASO operated by a single surgeon and assess the accuracy of echocardiography in identifying the coronary artery pattern before the ASO, this may lead to a better familiarization with the ASO. Methods: A retrospective study was conducted by operative and postoperative case note review of 125 patients from March 2015 to 2018. We assessed the outcomes of the arterial switch operation. Concomitant defects as atrial septal defects, patent ductus arteriosus and small ventricular septal defects were defined as the simple TGA and other defects were defined as the complex TGA. Coronary artery pattern determination by echocardiography prior to the surgery and during the operation was investigated, as well. 30-day mortality, post-operative neurologic complications, cardiac anatomic complications, arrhythmia, plasma lactate level and cardiopulmonary bypass time [CPB time] during the surgery were recorded. Results: The mean age and weight of the patients were 29.09 (1 - 180) days and 3506.48 (2400 - 9700) grams. Most of the patients (64%) were male. 105 (84%) of the patients had simple and 20 (16%) had complex TGA. Unusual coronary pattern during echocardiography was observed in 17 (13.6%) subjects and unusual coronary pattern during the operation was observed in 7 (5.6%) patients. The incidence of the major anatomical lesions was not significant. 20 (16%) had neurologic complications, including seizure in 14 (11.2%) patients, brain hemorrhage was found in 5 (4%) patients, as well as chorea and wrist drop in the remaining patients. Post-operative arrhythmia was observed in 16 (12.8%) patients. The mortality rate was 4% (5 patients). The CPB time was 202.73 ± 36.99 minutes. Conclusions: Our post-operative results of the ASO indicate excellent results. This signifies high experience and knowledge regarding this surgery.

Objective: Previous studies have demonstrated that both children and adult patients with a history of congenital heart disease (CHD) are at high risk for coronavirus disease 2019 (COVID-19) infection. This study investigates the status of COVID-19 infection among children undergoing surgical repair within the past 2 years.Methods: All alive patients operated on in a tertiary referral center between March 2018 and March 2020 were recruited in the present study. Detailed demographics, past medical and surgical history, and physical examination were reviewed for each patient. During the COVID-19 pandemic, data regarding the patient's status were collected by telephone survey from April 15 to April 30, 2020.Results: A total number of 210 patients are analyzed in this study. Participants' median age was 21.59 months [interquartile range (IQR) = 12–54.67], and 125 (59.5%) were female. The median interval between surgery and COVID-19 assessment was 305 days (IQR = 215–400). In addition, 67 (32%) patients used angiotensin receptor blocker (ARB)/angiotensin-converting enzyme (ACE) inhibitor (spironolactone and/or captopril). Sixteen patients (7.6%) were symptomatic and had positive chest CT results and/or RT-PCR compared to the previously reported prevalence of COVID-19 among the pediatric population (2.4% of children with p = 0.00012). Two patients were admitted to the intensive care unit (ICU); one patient was discharged 2 weeks later with acceptable status, and one patient died 2 days after ICU admission due to cardiac and respiratory arrest and myocarditis. The complexity of the underlying cardiac disorders was not different between patients with low risk (p = 0.522), suspicious patients (p = 0.920), and patients positive for COVID-19 (p = 0.234). The ARB/ACE inhibitor consumption was not associated with the COVID-19 infection [p = 0.527, crude odds ratio (OR) = 1.407, 95% CI = 0.489–4.052].Conclusion: Children with a history of previous CHD surgery are more susceptible to infections, especially those infections with pulmonary involvements, as the lung involvement could cause worsening of the patient's condition by aggravating pulmonary hypertension. The results of the current study indicate that these patients are more prone to COVID-19 infection compared to the healthy children population.

Background: A large proportion of infants with congenital heart defects (CHD) suffer from malnutrition. The aim of this study was to assess the impact of using energy- and nutrient-dense formula on weight gain in malnourished infants with CHD before surgery. Methods: This was a one arm, open label intervention study, conducted in the pediatric cardiology department of children’s medical center, Teheran, Iran. 49 infants with moderate/high risk cardiac defects who were undernourished (WFA z-score ≤ - 2) and were candidates for surgical repair were enrolled in this study. Infants on regular infant formula were switched completely to energy- and nutrient-dense formula. The infants were evaluated for growth parameters (weight and length) at enrolment and every 3 weeks thereafter at the center for a period of 12 weeks. Results: The average head circumference was 37.1+2.8 cm at baseline and 39.0+3.46 cm at the final assessment (p=0.079). The mean MUAC increased from 11.25+1.39 cm at baseline to 14.75+2.06 cm at the final assessment (p=0.001). The average intake of energy- and nutrient-dense formula was 148.24+214.737 Kcal/day (36.23+ 52.49 Kcal/kg/day) at study start and 455.4+177.21 Kcal/day (98.61 ± 38.27 Kcal/kg/day) at the end of the study. The WFA z-score improved significantly on each visit during the follow-up interval (pConclusion: The results of the current study highlight the efficacy of preoperative feeding with energy- and nutrient dense formula in improving weight gain of malnourished infants with CHD.reference number: IR.TUMS.VCR.REC.1396.3543

Background: Patients with congenital heart disease (CHD) are susceptible to mild malnutrition up to failure to thrive. The prevalence of malnutrition among patients with CHD is higher in developing countries. Many factors are considered to affect the nutritional status such as cyanosis. Objectives: This study aims to assess the prevalence and severity of malnutrition in patients with CHD prior to the surgical corrective or palliative repair. Methods: This study was performed by reviewing inpatient medical records and cardiac surgery databases of children with cyanotic CHD who underwent palliative or corrective surgery between March 2011 and March 2017. Patients’ age and height at the time of surgery, birth weight, duration of intensive care unit (ICU) stay and 30-day mortality were extracted and weight for age z score (WAZ), weight for length z score (WLZ) and length for age z score (LAZ) were calculated. Z scores above -1 were considered as normal, between -1 and -2 as mild, between -2 and -3 as moderate and below -3 as severe malnutrition. Results: In a total number of 639, the average age, weight and height were 16.688 ± 24.859 months, 7.509 ± 5.629 kilograms and 73.759 ± 95.869 centimeters, respectively. The average length of ICU stay was 8.36 ± 6.254 days and the 30-day mortality was 36 (5.7%). The average WAZ, LAZ, WLZ and BMI Z was -1.5 ± 1.69, -0.9 ± 2.38, -1.2 ± 3.97 and -1.4 ± 2.11, respectively. Regarding WAZ, LAZ, WLZ and BMI Z, 62.2%, 46.1%, 72.3% and 70.9% of patients had mild to severe forms of malnutrition, since the rate of malnutrition based on WAZ (P = 0.001), LAZ (P < 0.0001), WLZ (P < 0.0001) and BMI Z (P = 0.007), was significantly higher than normal subjects. Conclusions: The prevalence of mild to severe forms of malnutrition, based on different growth indices, for both cyanotics and acyanotics are higher than those reported in the other previous studies. These findings reflect the fact that cultural, genetic and racial differences of Iranians compared to others, cause malnutrition to be more frequent in Iranian CHD children. This calls for higher requirement of nutritional support for these patients.

Recent achievements in the genetic diagnosis of Dilated Cardiomyopathy (DCM) have disclosed rare variants in numerous genes encoding different types of myocardial proteins. However, the causative gene underlying the pathogenesis of about 60% of familial cases with DCM has not been identified. One novel gene introduced in 2016 for cardiac-restricted DCM is FLNC. In this study, we applied Whole Exome Sequencing (WES) and bioinformatics-based methods to a member of an extended non-consanguineous family with DCM history accompanied with fatal arrhythmia in at least four consecutive generations. We found a novel splice-site mutation in FLNC gene (c.2389+1G>A) which cosegregated with all symptomatic individuals in the family. Computational prediction software tools as well as RT-PCR method were used to evaluate the impact of the FLNC splice site mutation. This substitution leads to exon 15th donor-site disruption and exon skipping, which would result in a premature stop codon three aminocids downstream of the mutation site. The aberrantly mRNA transcript can induce nonsense-mediated mRNA decay. Although carrier individuals show remarkable variable expression regarding the severity of DCM as well as the disease age of onset, a highly penetrant fatal arrhythmia was found to be shared between them. We strongly suggest that the involvement of FLNC gene, due to haploinsufficiency, should be considered in familial cases with DCM, especially if accompanied with arrhythmia and increased incidence of sudden cardiac death.

Background: Mechanical PR Interval (MPRI) is an important parameter in the fetus as a surrogate for PR interval. Normal values of MPRI have been reported with controversial effects of Fetal Heart Rate (FHR) and Gestational Age (GA). However, the effect of HRcorrection on PR interval is unknown. Objectives: This study aimed to obtain the reference values of fetal MPRI in a large series of normal fetuses by pulsed-Doppler fetal echocardiography. This was done to determine the influence of fetal sex, Heart Rate (HR), GA, and maternal age on MPRI and to calculate the novel HR-Corrected Mechanical PR Interval (CMPRI) to investigate whether HR-correction of PR interval can decrease the influence of HR. Materials and Methods: This cross-sectional study was performed on 516 consecutive normal singleton fetuses. By extrapolation from Bazett’s formula, we corrected the MPRI for HR. Impact of fetal sex, HR, and GA on MPRI and CMPRI was studied. Mean ± standard deviation, 5th, 50th, 95th, and 99th percentiles of MPRI and CMPRI were also calculated. Then, the data were entered into Stata, version 12 and analyzed using t-test, ANOVA, and linear regression. Results: Reference values of MPPR and CMPRI were provided in four GA groups; i.e., 14 - 18, 19 - 22, 23 - 26, and 27 - 38 weeks. Fetal sex and maternal age had no influence on either MPRI or CMPRI. After adjustment for fetal sex, GA, and maternal age, there was a 0.14-millisecond (ms) decrease in MPRI and a 8.06-ms increase in CMPRI for every single increase in FHR. Additionally, adjusted linear regression model indicated a 0.43-ms increase in MPRI and a 2.53-ms increase in CMPRI per gestational week. The results of paired t-test showed no significant difference between fetal MPRI and neonatal PR interval. Conclusions: This study provided reference values for MPRI and CMPRI in fetus from 14 to 38 weeks of gestation from the 5th to the 99th percentile. The results also revealed significant correlations between both FHR and GA and MPRI and CMPRI. Furthermore, HR correction of MPRI did not add any advantage in terms of HR-independency of mechanical PR interval.

Neurocutaneous syndromes are heterogenous diseases that are diagnosed in the presence of skin and central nervous system disorders. Neurofibromatosis (NF) is one of these disorders, with autosomal dominant inheritance, that causes tumors that grow on nerves as well as other abnormalities such as skin changes and bone deformities. The most common form of NF is type I. A 6-year-old Iranian boy with neurofibromatosis was referred to the pediatric cardiology clinic due to a soft holosystolic murmur discovered on routine examination. The echocardiographic findings included a large intrapericardial, encapsulated echodense homogenous mass located in the posterior part of the pericardium, attached to the posterior aspect of the left atrium and left ventricle. The mass measured about 6.3×6.5×5.5cm and exerted a compressive effect on the left-side chambers, with mild mitral regurgitation and mild pericardial effusion. Magnetic resonance imaging confirmed these findings showing encasement of the left circumflex artery, while the open biopsy through a midsternotomy procedure showed a mildly cellular mesenchymal tumor composed of spindle cells suggestive of neurofibroma. Further resection of the mass was not performed because of the risk of coronary injury and the stable situation of the patient. Visceral involvement of neurofibroma is uncommon and rarely involves the heart. As shown in this case, besides the chance for involving the pericardium, despite its benign nature, this tumor sometimes shows unusual involvement of structures such as the coronary arteries.

Background: The Tei index is used to evaluate the overall performance of the right ventricle. The index can be measured with pulsed Doppler echocardiography (PW) and tissue Doppler imaging (TDI). Some studies show that severe pulmonary valve regurgitation (PR) can influence the Tei index calculated by the PW method. Objectives: The purpose of this study was to compare PW and TDI in calculating the Tei index in PR patients following TOF reconstruction. Methods: We evaluated 21 patients with severe PI who were reconstructed and 21 age-matched normal children. All the children went through PW or TDI. The intensity of Sa, Ea, Aa, IVCT, and the Tei index were calculated. Results: The mean age of the patients and controls was 3.8 ± 3.2 and 3.7 ± 2.7 years, respectively. There was no difference in the Tei index between healthy children and TOF patients calculated by the PW method (0.30 ± 0.10 vs. 0.35 ± 0.06; P = 0.059). However, TOF patients had a lower intensity of Sa, Ea, and Aa than healthy children. Furthermore, the isovolumic interval of both IVCT and IVRT was longer in TOF patients than in healthy children (43.53 ± 8.82 vs. 25.77 ± 10.14 and 87.73 ± 10.91 vs. 68.36 ± 8.96, respectively; P = 0.001 for both) but the S duration had no difference between the groups (265.1 ± 18.1 in TOF patients vs. 266.8 ± 28.0 in controls). The Tei index calculated by TDI was significantly higher in TOF patients than in healthy children (0.50 ± 0.10 vs. 0.36 ± 0.06; P = 0.001). Moreover, the Tei index calculated by TDI was higher than the Tei index calculated by PW in TOF patients (0.50 ± 0.10 vs. 0.30 ± 0.10; P = 0.001). Conclusions: TDI is a more accurate method for calculating the Tei index for evaluating the overall performance of the right ventricle in PR patients after TOF reconstruction, and the Tei index calculated through PW had limitations for this purpose.

Background: To normally grow and develop, children with congenital heart diseases (CHD) in the hypermetabolic state need 50% more energy than healthy ones. Objectives: This study aimed to investigate the prevalence of malnutrition and its association with other factors among the non-syndromic acyanotic patients with CHD undergoing palliative or corrective surgery. Methods: A retrospective study of medical records of 812 children with acyanotic congenital heart disease undergoing palliative or corrective surgery was performed from March 2011 to March 2017. Collected data consisted of the age at the time of the surgery, gender, weight at the time of the surgery, height at the time of the surgery, birth weight, length of ICU stay, and 1-year mortality. The WAZ, WLZ, LAZ, and BMI Z-scores were calculated based on World Health Organization (WHO) standards. We classified the Z-scores into 4 groups, including normal (Z-scores > -1), mild (-2 to > -1), moderate (-3 to > -2), and severe (< -3) malnutrition groups. Results: Total amount of 812 patients, 375 (46.2%) were female and 437 (53.8%) male, participated in this study. The average age, weight, and height at the time of the surgery were 23.52 + 29.38 months, 9.086 + 6.71 kilograms, and 76.93 + 23.37 centimeters, respectively. Moreover, 68.7% and 66.4% of the patients suffered from mild to severe forms of malnutrition based on WAZ and WLZ, respectively (P value < 0.0001, 0.025). There was no significant difference between males and females in WAZ, WLZ, LAZ and, BMIZ (P value: 0.154, 0.265, 0.965, and 0.667, respectively). Generally, in acyanotic defects, we found that more severe malnutrition causes an increment in length of ICU stay (P value = 0.001) and lesser birth weight has a significant relationship with the severity of growth failure in infancy or childhood (P value < 0.0001). Conclusions: In our study, the high prevalence of the malnutrition and related complications during and after surgical repair shows the importance of nutritional support and interventions in patients with CHD.

Objectives: To evaluate fetal cardiac changes in gestational diabetic mothers, compared to healthy ones by means of different indices and to determine which index can first represent the alterations. Methods: The study was conducted as an observational cross-sectional study, including 25 pregnant women with gestational diabetes as the cases and 50 healthy pregnant women as the controls. The preload index, left and right side myocardial performance index (MPI), Interventricular septal hypertrophy, the left and right side cardiac output were assessed in all the patients. Results: The gestational ages were 31.65 ± 8.02 and 31.64 ± 5.37 weeks in case and control group respectively, without any significant difference. Both of the left and right ventricular MPI did not differ statistically between the case and controls. The cases had a greater Interventricular septal hypertrophy but the cardiac output was similar. The preload index was higher in the fetuses of the gestational diabetic mothers. Conclusions: In our study, the MPI did not show any difference between the fetuses of the gestational diabetic mothers and non-diabetic ones; but, fetuses of gestational diabetic mothers had a greater value of PLI, representing early diastolic function changes in right heart even before the overt heart failure occurred. This could be a sign of vasculopathy in gestational diabetic mothers.

Objectives: Coronary artery (CA) involvement is the most well known complication of Kawasaki disease (KD). Previous studies have suggested that QT dispersion has a predictive value in diagnosing cardiac ischemia, ventricular arrhythmia, and sudden cardiac death. However, limited data exits regarding the application of QT dispersion in KD. Therefore, we sought to determine whether there is a relationship between QT dispersion and CA involvement in patients with KD. Methods: We performed a cross-sectional study of all consecutive patients with KD who were followed-up at the Pediatric Rheumatology Department (Pediatrics Center of Excellence affiliated to Tehran University of Medical Sciences, Tehran, Iran) from September 2013 to November 2015. Patients who met the criteria for KD, based on the American Heart Association guideline, were enrolled in the study. We collected data regarding patients’ demographics, clinical manifestations, laboratory, and echocardiographic findings. Results: A total of 70 KD patients were identified, including 43 males (61.4%) and 27 females (38.6%). The median age of patients was 21.0 (11.0–48.0) months. We found statistically significant differences between age, gender, and platelet count among patients with and without CA involvement (p < 0.050). Median corrected QT dispersion in patients with CA involvement calculated from 12 leads in the acute phase was significantly higher compared to the non-CA involvement group (108.0 (89.5–138.5) ms vs. 63.0 (54.0–74.5) ms, respectively (p < 0.001)). Conclusions: Prolonged QT dispersion (corrected or non-corrected) during the acute and convalescence phases in patients with KD is associated with coronary involvement.

A 13-year-old girl, as a known case of type III Gaucher disease, was referred to us for a cardiac assessment. Our investigations revealed wall thickening and calcification in the ascending thoracic aorta, transverse arch, and isthmus. Calcification was also present in the proximal portion of the brachiocephalic trunk while the osteal narrowing of right common carotid was also notable. The other finding included isolated thrombocytopenia. We decided to perform surgery after two months of enzyme replacement therapy.

Objectives: Ventricular septal defect (VSD) includes 40% of congenital heart diseases. Surgical closure of VSD is the most common procedure in pediatric cardiac surgery. Weight is the most restrictive factor for performing the surgery as it complicates the operation and post-operative care. The aim of this study was to determine the results of the surgery for the patients undergoing this procedure with the weight under 5 kilograms and to catch a good insight into performing surgery at lower age and weight. Methods: A retrospective study was conducted by operative and postoperative case note review of 54 patients from March 2014 to 2017. We assessed the outcomes of the early surgical closure of the ventricular septal defects. Results: In our study, the weight was 4.4 + 0.61 kilograms and the age was 5.72 + 2.22 months. Post-surgical result by echocardiography showed reduced immediate pulmonary artery pressure in all patients, other post-surgical evaluations showed 1 (1.9%) mild, 1 (1.9%) moderate to severe pericardial effusion, 1 (1.9%) first degree AV Block, 2 (3.7%) right bundle branch block and 4 (7.4%) complete heart block leading to permanent pace maker implantation. Significant myocardial stunning (ejection fraction < 40%) was noted in 6 (11.11%). The patient mortality in the first 30 days was zero and there was no post-operative immediate endocarditis, seizure, bleeding or cardiac arrest. Conclusions: Observations can prove increased ability, knowledge and techniques of the surgeons operating VSDs. Based on the outcomes, earlier surgical VSD closure is recommended.

A 30-month-old girl was referred to our clinic because of a large ASD secundum and severe pulmonary valve stenosis. Due to her clinical and paraclinical situation we decided to perform the surgery. The patient had no other symptoms except for those related to ASD. During the surgery we found a mass with its satellite nodule on the tricuspid valve. Histopathological examination of the mass revealed larval elements and infiltration of eosinophils.

Background Despite high effectiveness of Anthracycline as a potent antineoplastic agent, its-related cardiothoxicity is the most notorious complication. The purpose of our study was to assess the value of using different methods (LVEF, E, E’, A and Tei index versus global longitudinal strain) for detection of early cardiac changes by measuring them before and one month after the Anthracycline administration in a cross-sectional cohort study. Methods This cross-sectional study was performed on 22 new diagnosed cancer patients aged 18 years or younger who referred to the children Medical center in Tehran in 2016 as the cases and also 22 age-matched healthy children who referred to the center because of any non-cardiac reasons as the control. All participants were assessed to determine the left ventricular functional indices before and also one month after starting the therapeutic regimen containing Anthracycline. Results Among all parameters assessed by echocardiography, only the mitral annular peak systolic velocity (Sm) significantly reduced after administrating Anthracycline compared to before that. Data for patients and the control group showed no statistical significant differences before the therapy as well. Conclusions Our findings show that evaluating Sm is most useful for early detection of cardiac changes. This may be due to our limitation of small cohort studies and also the short interval after the drug administration; although this was related to the main goal of our study.

Background: Doppler - derived fetal pulmonary artery acceleration time (PAAT) and acceleration - to - ejection time ratio (AT/ET) are important as predictors of a variety neonatal pulmonary diseases. The evaluation of PAAT and PA AT/ET are meaningful when simultaneous right and left heart studies are done. The unique cardiovascular physiology in the fetus, as the only period of life with physiologic systemic pulmonary hypertension, overemphasizes the significance of simultaneous study. However, studies on comparative fetal velocitometry of PA and aorta are scarce. Objectives: The aims of this study were to provide reference values for peak systolic velocity (PSV), pulsatility index (PI), acceleration time (AT), ejection time (ET) and AT/ET ratio of PA and aorta in the singleton pregnancies with healthy fetuses. We compared these Doppler parameters of PA and aorta. Methods: A cross - sectional study was performed on 146 fetuses. We measured PSV, PI, AT, ET and AT/ET in the PA and aorta and compared the values. We evaluated the correlation between these parameters and the fetal gestational age (GA). Results: Mean ± SD of gestational age of fetuses were 21 ± 4 weeks. PSV, AT and AT/ET of PA and aorta increased with gestational age. PSV, PI, AT and AT/ET were significantly lower in the PA relative to the aorta. Conclusions: Despite equal pressures in PA and aorta in the fetal period, the PSV, PI, AT and AT/ET are lower in the PA. This study indicates that, in contrast to children and adults, PA pressure is not the major determinant of fetal PAAT.

The prevalence of fetal arrhythmia is about 1% to 3% of all pregnancies and they are mostly benign. This report describes fetal ectopic atrial tachycardia (EAT) diagnosed in 31 weeks of gestation. The arrhythmia did not respond to transplacental therapy; therefore, cesarean section was done and arrhythmia was controlled by propranolol. This case showed effectiveness of rate control strategy by administration of propranolol.

Objective Tricuspid atresia (TA) is a rare life-threatening form of congenital heart defect (CHD). The genetic mechanisms underlying TA are not clearly understood. According to previous studies, the endocardial cushioning event, as the primary sign of cardiac valvulogenesis, is governed by several overlapping signaling pathways including Ras/ ERK pathway. RASA1, a regulator of cardiovascular development, is involved in this pathway and its haploinsufficiency (due to heterozygous mutations) has been identified as the underlying etiology of the autosomal dominant capillary malformation/arteriovenous malformation (CM/AVM). Materials And Methods In this prospective study, we used whole exome sequencing (WES) followed by serial bioinformatics filtering steps for two siblings with TA and early onset CM. Their parents were consanguineous which had a history of recurrent abortions. Patients were carefully assessed to exclude extra-cardiac anomalies. Results We identified a homozygous RASA1 germline mutation, c.1583A>G (p.Tyr528Cys) in the family. This mutation lies in the pleckstrin homology (PH) domain of the gene. The parents who were heterozygous for this variant displayed CM. Conclusion This is the first study reporting an adverse phenotypic outcome of a RASA1 homozygous mutation. Here, we propose that the phenotypic consequence of the homozygous RASA1 p.Tyr528Cys mutation is more serious than the heterozygous type. This could be responsible for the TA pathogenesis in our patients. We strongly suggest that parents with CM/AVM should be investigated for RASA1 heterozygous mutations. Prenatal diagnosis and fetal echocardiography should also be carried out in the event of pregnancy in heterozygous parents.