Spectrum Of Congenital Heart Disease Research Articles

BeGraft Aortic Stents: A European Multi-Centre Experience Reporting Acute Safety and Efficacy Outcomes for the Treatment of Vessel Stenosis in Congenital Heart Diseases.

Stent implantation has become the preferred method of treatment for treating vessel stenosis in congenital heart diseases. The availability of covered stents may decrease complications and have an important role in the management of patients with complex anatomy. This study aims to evaluate the feasibility and safety of the pre-mounted cobalt-chromium stent-graft-covered ePTFE Aortic BeGraft in a broad spectrum of vascular lesions. This is a multicenter retrospective results analysis of 107 implanted BeGraft stents between 2016 and 2022 in six different European centers. One hundred and four patients with a mean age of thirteen years (range 1-70 years) and with the body weight of 56.5 kg (range 11-115 kg) underwent the BeGraft stent implantation. Stents were implanted in the following conditions: aortic coarctation (74 patients), RVOT dysfunction (12 patients), Fontan circulation (7 patients), and miscellaneous (11 subjects with complex CHD). All the stents were implanted successfully. The median stent diameter was 16 mm (range 7-24 mm), and the median length was 39 mm (range 19-49 mm). Major complications occurred in five subjects (4.7%). During a median follow-up of fourteen (1-70) months, stents' re-dilatation was performed in five patients. The BeGraft stent can be used safely and effectively in a wide spectrum of congenital heart diseases. Whether these good results will be stable in the longer term still needs to be investigated in a follow-up given its recent introduction into clinical practice, in particular regarding stent fracture or neointimal proliferation.

The detailed profile of congenital heart diseases in 254 children with Down syndrome in Saudi Arabia

BackgroundDown syndrome is the most common chromosomal abnormality in humans. It is associated with several congenital anomalies, including a spectrum of congenital heart diseases. Understanding the true prevalence and distribution of congenital heart diseases is essential for health resource planning, outcomes, and family counseling.This study aimed to assess the prevalence and distribution of congenital heart disease in children with Down syndrome. It is a retrospective cohort review that included all patients treated at King Abdulaziz University Hospital. Frequencies were estimated using the SPSS software and comparisons were made using Student’s t test.ResultsThe ages of the 254 subjects ranged from less than 1 year to 53 years. Of these, 44.5% were female and 40.6% were Saudi nationals. Congenital heart disease was present in 66.5% with a significant difference between Saudi nationals 44.6%) and non-Saudi nationals 71.5% (P = 0.01). The atrioventricular septal defect was the most common pathology, representing 33.1% of all congenital heart diseases followed by perimembranous ventricular septal defect 18.9%, and right ventricular pathology 10.2%.ConclusionThe prevalence of congenital heart diseases in Saudi children with Down Syndrome is similar to that reported worldwide. Septal defects and right-sided pathologies are the dominant forms of congenital heart diseases, with atrioventricular septal defect and perimembranous ventricular septal defect representing the most common pathologies.

Alagille Syndrome and Associated Cardiac Pathologies: A Comprehensive Exploration of the Interplay between Genetic Factors and Cardiovascular Manifestations

Alagille Syndrome (ALGS) stands as a multifaceted genetic disorder renowned for its distinctive cholestatic liver disease and characteristic facial features. Beyond the hepatic implications, ALGS has been increasingly recognized for its intricate association with a spectrum of congenital heart diseases, presenting a challenging clinical scenario. This article elucidates the complex interrelation between Alagille Syndrome and various cardiac anomalies, delving into the underlying genetic mechanisms and clinical implications. By synthesizing current research, we aim to enhance the understanding of clinicians and researchers regarding the nuanced cardiovascular manifestations of Alagille Syndrome, paving the way for improved diagnostic strategies and targeted interventions.

Generation and characterization of a human induced pluripotent stem cell line heterozygous for a NOTCH1 mutation (NCHi014-A)

NOTCH1 signaling is crucial for cardiovascular development. Numerous studies have identified heterozygous NOTCH1 loss of function and missense variants associated with a spectrum of congenital heart diseases (CHD). We generated induced pluripotent stem cells (iPSC) from a healthy individual to develop a model for NOTCH1+/- iPSC to study the molecular pathogenesis of CHD. NOTCH1+/-iPSC (NCHi014-A) have normal morphology and karyotype, are identical to the parental cell line, express pluripotency markers and have the ability to differentiate to the three germ layers. NOTCH1+/- iPSC can be used as a tool to study the cellular and molecular mechanisms underlying NOTCH1-associated human CHD.

The spectrum of congenital heart defects in neonates of diabetic mothers

Introduction: Insulin-dependent diabetes mellitus (IDDM) in a mother is considered a risk factor for congenital malformation, including congenital heart diseases. Many studies signify a five to six times increased frequency of congenital heart diseases in neonates born from insulin-dependent diabetic mothers. This study aimed to identify the spectrum of congenital heart diseases (CHDs) in neonates born from insulin-dependent diabetes mellitus (IDDM) mothers. Methods: Between April 2019 and March 2021, a descriptive cross-sectional study involved 120 consecutive neonates aged 0-28 days of mothers with insulin-dependent diabetes mellitus (IDDM) at Maiwand Teaching Hospital, Kabul University of Medical Sciences. Neonates born to non-diabetic mothers were excluded. IDDM refers to mothers using Insulin upon admission to control blood glucose. CHD encompasses various heart defects affecting function. Family and maternal history were noted, focusing on health issues and delivery details. Neonatal mothers' ages ranged from 23 to 45 (mean 33), with diabetes onset spanning 2.5 to 25 years. Pediatric cardiologists conducted physical and echocardiographic exams. All CHD forms were documented using 2D echocardiography and Doppler studies (Sono Ace X-6 Machine). Result: 120 consecutive neonates born to mothers with insulin-dependent diabetes mellitus (IDDMs) were investigated during the two-year study period. Of them, 18 (15%) had congenital heart abnormalities. The prevalence of solitary and multiple CHD was 66.6 percent (12 patients) and 33.3 percent (6 patients) in the 18 infants born from IDDMs. The most prevalent isolated defects were PDA (22.2%) and Ventricular septal defect (16.6%). The most common multiple CHDs (16.6 percent) were PDA and ASD. PDA + ASD (16.6%) and VSD + PDA were the most frequent correlations with CHD (11.1 percent). Conclusion: Maternal insulin-dependent diabetes mellitus is an important risk factor for congenital heart disease. Careful assessment and early diagnosis of CHD in this high-risk group are very important in a pediatric population. Expansion of prenatal screening programs for CHDs in mothers suffering from insulin-dependent diabetes mellitus is necessary. Keywords: congenital heart diseases; diabetic mothers; insulin dependent; neonates

Differences in Quality of Life in Children Across the Spectrum of Congenital Heart Disease

To create complexity groups based upon a patient's cardiac medical history and to test for group differences in health-related quality of life (HRQOL). Patients 8-18 years with congenital heart disease (CHD) and parent-proxies from the Pediatric Cardiac Quality of Life Inventory (PCQLI) Testing Study were included. Outcome variables included PCQLI Total, Disease Impact, and Psychosocial Impact scores. Using a patient's medical history (cardiac, neurologic, psychological, cognitive diagnosis), latent class analysis (LCA) was used to create CHD complexity groups. Covariates included demographics and burden of illness (number of: school weeks missed, physician visits in the past year, daily medications). Generalized estimation equations tested for differences in burden of illness and patient and parent-proxy PCQLI scores. Using 1,482 CHD patients (60% male; 84% white; age 12.3±3.0 years), LCA estimates showed four distinct CHD complexity groups (Mild, Moderate 1, Moderate 2, and Severe). Increasing CHD complexity was associated with increased risk of learning disorders, seizures, mental health problems, and history of stroke. Greater CHD complexity was associated with greater burden of illness (p<0.01) and lower patient- and parent-reported PCQLI scores (p<0.001). LCA identified four CHD complexity groupings. Increasing CHD complexity was associated with higher burden of illness and worse patient- and parent-reported HRQOL.

Spectrum of Congenital Heart Diseases in Children at a Tertiary Care Centre: A Cross-Sectional Study

Introduction: A gross anatomical anomaly of the heart or intrathoracic great vessels that is actually or potentially functionally significant is referred to as congenital heart disease (CHD). One of the main reasons for newborn mortality is CHDs. A significant hospital-based study from India estimates that 3.9 out of every 1000 live babies are affected by congenital heart disease. Thus, we conducted this research with the aim to study the prevalence, age-wise distribution, and clinical spectrum of congenital heart disease (CHD) in a tertiary care medical college hospital in Maharashtra. Methodology: This was a retrospective, descriptive, cross-sectional study carried out from March 2020 to March 2022 at a tertiary care hospital and medical college. The study included records of all discharged live births (CHD patients) as well as all in and outpatients between the ages of 0-18 years. For the diagnosis of CHD, a definition proposed by Mitchell et al. was applied. Results: CHD was detected in 9 out of 645 live births in the hospital during the study period. 168 children were diagnosed to be having some type of CHD. Ventricular septal defect was the most common heart lesion 43 (25.6%). Maximum number of cases were seen in 0-3 years age group (86.3%). Conclusion: The present study’s finding indicates that the prevalence of CHD in Maharashtra is less compared to the prevalence reported in some other studies worldwide. However, it is a serious problem, which requires immediate attention for the improvement of diagnostic and therapeutic facilities which is accessible to the common man.&#x0D;

RASopathies and cardiac manifestations.

As binary switches, RAS proteins switch to an ON/OFF state during signaling and are on a leash under normal conditions. However, in RAS-related diseases such as cancer and RASopathies, mutations in the genes that regulate RAS signaling or the RAS itself permanently activate the RAS protein. The structural basis of this switch is well understood; however, the exact mechanisms by which RAS proteins are regulated are less clear. RAS/MAPK syndromes are multisystem developmental disorders caused by germline mutations in genes associated with the RAS/mitogen-activated protein kinase pathway, impacting 1 in 1,000-2,500 children. These include a variety of disorders such as Noonan syndrome (NS) and NS-related disorders (NSRD), such as cardio facio cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML, also known as LEOPARD syndrome). A frequent manifestation of cardiomyopathy (CM) and hypertrophic cardiomyopathy associated with RASopathies suggest that RASopathies could be a potential causative factor for CM. However, the current supporting evidence is sporadic and unclear. RASopathy-patients also display a broad spectrum of congenital heart disease (CHD). More than 15 genes encode components of the RAS/MAPK signaling pathway that are essential for the cell cycle and play regulatory roles in proliferation, differentiation, growth, and metabolism. These genes are linked to the molecular genetic pathogenesis of these syndromes. However, genetic heterogeneity for a given syndrome on the one hand and alleles for multiple syndromes on the other make classification difficult in diagnosing RAS/MAPK-related diseases. Although there is some genetic homogeneity in most RASopathies, several RASopathies are allelic diseases. This allelism points to the role of critical signaling nodes and sheds light on the overlap between these related syndromes. Even though considerable progress has been made in understanding the pathophysiology of RASopathy with the identification of causal mutations and the functional analysis of their pathophysiological consequences, there are still unidentified causal genes for many patients diagnosed with RASopathies.

Spectrum of Congenital Heart Disease in Children with Down's Syndrome

Background: Down syndrome is the most common chromosomal disorder and most common genetic cause of mental retardation. Congenital heart disease (CHD) is an important cause of morbidity and mortality in children with Down's syndrome. Objective: To determine the frequency and types of congenital heart diseases in children with Down syndrome and to relate it with consanguinity. Material and Methods: This Cross-sectional study was carried out at Bacha Khan Medical Complex / Gajju Khan Medical College, Swabi, from January 2019-December 2020. Children less than 12 year's age with Down syndrome were enrolled in the study. Echocardiography of all these children was done and presence and type of CHD was noted.Results: Our study included 95 children with diagnosis of Down syndrome. The mean age was 56.12±41.89 months. 40% were males. Mother's mean age was 33.04±4.2 years. Mothers having age = 35 years old were 30.5%. Parents having consanguineous marriage were 33.7%. The diagnosis of major congenital heart defect was in 37.9%. Out of 36 CHD patients the type of congenital heart lesion was as follows: 36.11% had AVSD, 25% had ASD; 30.5% had VSD; 5.55% had tetralogy of Fallot and 2.78% had PDA. Children with down syndrome with CHD had older mothers &lt;0.05. Mothers with consanguineous marriages had a greater proportion of CHD children; p&lt;0.05. Conclusion: Approximately 1/3rd Down syndrome children had congenital heart disease. The commonest lesion was AVSD followed by VSD, ASD, tetralogy of Fallot and PDA. Consanguineous marriages are associated with a greater frequency of CHD in Down children.Keywords: Down syndrome, congenital heart disease, Echocardiography.

Spectrum of congenital heart disease in Nepal from 2002-2022: A systematic review and meta-analysis.

Congenital heart diseases are recognized as public health concerns worldwide and Nepal is no exception. This study aims to study congenital heart disease in Nepal on grounds of burden, commonest type, common presentations, and associated noncardiac anomalies so that its spectrum can be known for prompt diagnosis and adoption of screening protocols. Relevant articles were searched in electronic databases using appropriate search terms and Boolean operators. Data were extracted in Excel and analyzed in Comprehensive Meta-Analysis Software. The proportion was used as an effect measure and a fixed or random-effect model was used as per the heterogeneity. Forest plots were used to give visual feedback. A total of nine studies were included in the qualitative and quantitative synthesis after a rigorous screening of imported studies. The prevalence of congenital heart disease was 0.7% (Proportion: 0.007; CI: 0.001-0.035; I2: 99.263%). The burden of atrial septal defect was 32.1%, ventricular septal defect was 31.1%, patent ductus arteriosus was 12.6% and Tetralogy of Fallot was 7.3%. The most common presentations were respiratory tract infection (54.7%), developmental delay (49.8%), difficulty in breathing (44.5%), failure to thrive (17.1%), and cyanosis (15.9%). The prevalence of congenital heart disease in Nepal was 0.7% and the frequency of male patients was higher. The atrial septal defect was the commonest on the whole, while, Tetralogy of Fallot was the commonest among cyanotic variety. Respiratory tract infection was frequently seen at presentation and the most commonly associated noncardiac anomaly was the cleft palate.

Cor triatriatum with Partial Anomalous Pulmonary Venous Connection: Role of Multimodal Imaging

Abstract Both cor triatriatum (CorT) and partial anomalous pulmonary venous connection (PAPVC) come under the rare spectrum of congenital heart diseases. These entities may coexist in a patient or may appear independent of each other. The diagnosis is established routinely by echocardiography. Here, we describe the case of a 45-year-old female presenting with exertional dyspnea and palpitations. She was diagnosed to have CorT in the preoperative echocardiography; later, intraoperatively, transesophageal echocardiography revealed the additional presence of PAPVC with CorT. This case report highlights the limitations of echocardiographic findings in the patient and the importance of multimodal imaging techniques in such situations.

The Spectrum of Congenital Heart Disease in Children in the Andaman and Nicobar Islands: A Five-Year Retrospective Study.

Introduction: Congenital heart disease (CHD) is an abnormality in the structure or function of the cardio-circulatory system present at birth but more often diagnosed subsequently. CHD is the most common (28%) major congenital anomaly and thus signifies a major global health problem. The primary objective is to estimate the frequency and pattern of CHD in children in the Andaman and Nicobar Islands (India).Methods: We did a hospital-based retrospective observational study. The hospital case records of all children belonging to the age group of 0 to 12 years with newly diagnosed CHD were reviewed for the five years from January 1, 2016 to December 31, 2020. The clinical, demographic, and echocardiogram details were retrieved, and descriptive analysis was done using the Statistical Package for the Social Sciences (SPSS) for Windows Version 26 (IBM, Chicago, USA).Results: A total of 201 (12.8 per 1000) children were newly diagnosed with CHD (out of a total of 15592 children). There were 110 (54.7%) boys and 91 (45.3%) girls in the age group of 0 to 144 months (mean ± SD: 13.86±27.13). The ventricular septal defect (VSD) is the most common congenital heart defect, accounting for 25.4% of all CHD cases. The most common cyanotic CHD was tetralogy of Fallot (TOF), comprising 8% of the total cases.Conclusion: The spectrum of CHD in our study was largely similar to pre-existing literature. Although most of the CHDs were detected during infancy, a higher proportion of complex lesions in our study group resulted in adverse outcomes, even in surgically managed cases.

Prospective Assessment of Coronary Artery Flows Before and After Cardiopulmonary Bypass in Children With a Spectrum of Congenital Heart Disease.

Normative data for the effect of cardiopulmonary bypass (CPB) on coronary artery Doppler velocities by transesophageal echocardiography in paediatric patients with congenital heart disease (CHD) are lacking. The objective of the study was to prospectively examine the effects of CPB on coronary artery flow patterns by transesophageal echocardiography before and after CPB in children with CHD. All cases undergoing CHD surgery at the Hospital for Sick Children, Toronto, were eligible. The excluded cases included Norwood operation, heart transplantation, or weight <2.5 kg. Coronary Dopplers and coronary flow reserve (CFR) for the right coronary artery (RCA) and left anterior descending (LAD) were obtained. Multivariable analyses using linear regression models were performed, adjusted for age and cross-clamp time. From May 2017 to June 2018, 69 children (median age at surgery: 0.7 years, interquartile range [IQR]: 0.4-3.7 years; median weight: 7.4 kg, IQR: 5.8-13.3 kg) were included. They were grouped into shunt lesions (N= 26), obstructive lesions (N= 26), transposition of the great arteries (N= 5), and single ventricle (N= 12). N= 39 (57%) were primary repairs, and 56 (81%) had 1 CPB run. For RCA and LAD peak velocities, there was an increase from pre- to post-CPB in RCA peak 39 cm/s (IQR: 30-54 cm/s) to 65 cm/s (IQR: 47-81 cm/s), P< 0.001, mean CFR 1.52 (IQR: 1.25-1.81), and LAD peak 49 cm/s (IQR: 39-60 cm/s) to 70 cm/s (IQR: 52-90 cm/s), P < 0.001, mean CFR 1.48 (IQR: 1.14-1.77). Coronary flow velocities increase from pre- to post-CPB in congenital heart lesions. CFR is consistent across all lesions but is relatively low compared with the adult population.

Mutation spectrum of congenital heart disease in a consanguineous Turkish population.

BackgroundsWhile many studies agree that consanguinity increases the rate of congenital heart disease (CHD), few genome analyses have been conducted with consanguineous CHD cohorts.MethodsWe recruited 73 CHD probands from consanguineous families in Turkey and used whole‐exome sequencing (WES) to identify genetic lesions in these patients.ResultsOn average, each patient had 6.95 rare damaging homozygous variants, 0.68 of which are loss‐of‐function (LoF) variants. Seven patients (9.6%) carried damaging homozygous variants in five causal CHD genes. Six of those patients exhibited laterality defects (six HTX and one D‐TGA). Three additional patients (4.1%) harbored other types of CHD‐associated genomic alterations, which overall explained 13.7% (10/73) of the cohort. The contribution from recessive variants in our cohort is higher than 1.8% reported from a cohort of 2871 CHD subjects where 5.6% of subjects met the criteria for consanguinity.ConclusionsOur WES screen of a Turkish consanguineous population with structural CHD revealed its unique genetic architecture. Six of seven damaging homozygous variants in CHD causal genes occur in the setting of laterality defects implies a strong contribution from consanguinity to these defects specifically. Our study thus provided valuable information about the genetic landscape of CHD in consanguineous families in Turkey.

Right ventricular outflow tract anomalies: Neonatal interventions and outcomes

Right ventricular outflow tract (RVOT) anomalies comprise a wide spectrum of congenital heart disease, typically characterized by obstruction to flow from the right ventricle to pulmonary arteries. This review highlights important considerations surrounding management strategy as well as clinical outcomes for the neonate with RVOT anomaly, including: pulmonary atresia with intact ventricular septum, congenital pulmonary valve stenosis, tetralogy of Fallot, and Ebstein anomaly with anatomic or physiologic RVOT obstruction.

Long-Term Risk of Heart Failure-Related Death and Heart Transplant After Congenital Heart Surgery in Childhood (from the Pediatric Cardiac Care Consortium)

We aimed to describe the longitudinal risk of advanced heart failure (HF) leading to death, heart transplantation, or ventricular assist device (VAD) placement after congenital heart surgery (CHS) and how it varies across the spectrum of congenital heart disease. We linked the records of patients who underwent first CHS in the Pediatric Cardiac Care Consortium between 1982 and 2003 with the United States National Death Index and Organ Procurement and Transplantation Network databases. Primary outcome was time from CHS discharge to HF-related death, heart transplant, or VAD placement, analyzed with proportional hazards models accounting for competing mortality. In 35,610 patients who survived a first CHS, there were 799 HF deaths, transplants, or VADs over a median of 23 years (interquartile range, 19 to 27). Cumulative incidence at 25 years was 2.3% (95% confidence interval [CI] 2.1% to 2.4%). Compared to mild 2-ventricle defects, the adjusted subhazard ratio for moderate and severe 2-ventricle defects was 3.21 (95% CI 2.28 to 4.52) and 9.46 (95% CI 6.71 to 13.3), respectively, and for single-ventricle defects 31.8 (95% CI 22.2 to 45.6). Systemic right ventricle carried the highest risk 2 years after CHS (subhazard ratio 2.76 [95% CI 2.08 to 3.68]). All groups had higher rates of HF-related death compared with the general population (cause-specific standardized mortality ratio 56.1 [95% CI 51.0 to 61.2]). In conclusion, the risk of advanced HF leading to death, transplantation, or VAD was high across the spectrum of congenital heart disease. While severe defects carry the highest risk, those with mild disease are still at greater risk than the general population.

Homograft durability after correction of pulmonary atresia and ventricular septal defect with or without systemic pulmonary collateral arteries

BackgroundPulmonary atresia and ventricular septal defect (PA-VSD), with or without systemic pulmonary collateral arteries (SPCAs), represents a complex anatomic and surgical spectrum of congenital heart disease. Currently, there is limited evidence on homograft durability after complete correction, which potentially could be affected by anatomic differences in pulmonary vasculature. MethodsThis retrospective single-center study included all 69 consecutive PA-VSD patients (46 with SPCAs, 23 without SPCAs) operated on between 1978 and 2018. The primary interest was in homograft durability after complete repair. Longitudinal echocardiographic homograft function and right ventricular systolic pressure were analyzed with linear mixed-effects models. ResultsThe median duration of follow-up was 20 years. Of the 46 patients with SPCAs, 37 (80.4%) underwent biventricular correction at a median age of 2.7 years (interquartile range [IQR], 1.8-6.3 years). Two patients are currently awaiting unifocalization and correction. All 23 patients without SPCAs underwent successful complete correction at a median age of 1.6 years (IQR, 1.1-3.6 years). Freedom from any reintervention after 20 years was 15%. When a homograft was used during correction, freedom from homograft replacement after 20 years was comparable in the 2 groups (P = .925), at 32 ± 11% in the SPCA group and 32 ± 13% in the non-SPCA group. Indications for homograft replacement were isolated stenosis (n = 7; 46.7%), isolated regurgitation (n = 3; 20.0%), and mixed stenosis and regurgitation (n = 5; 33.3%) in the SPCA group and isolated stenosis (n = 8; 88.9%) and stenosis and regurgitation (n = 1; 11.1%) in the non-SPCA group. Peak homograft gradient was significantly (P = .0003) higher in patients without SPCA, with a comparable rate of progression in the 2 groups. However, the prevalence of severe pulmonary regurgitation (PR) was higher in patients with SPCAs, estimated at 35% at 10 years, compared with 15% in patients without SPCAs. ConclusionsHomografts used for right ventricular outflow tract reconstruction in patients with PA-VSD, either with or without SPCAs, have similar limited durability. Repeated reintervention is common, and careful follow-up with attention to severe PR is warranted.

The Spectrum of Congenital Heart Diseases Operated at Shahid Gangalal National Heart Center in the last 5 Years.

Background and Aims: The spectrum of congenital heart diseases (CHD) presenting for surgery to any cardiac center varies depending upon the geographical location of the center. This study is aimed to reveal the spectrum of CHD operated at a tertiary level cardiac center of Nepal.&#x0D; Methods: This is a retrospective study conducted at the Department of Cardiovascular Surgery at Shahid Gangalal National Heart Center (SGNHC), Kathmandu, over a period of five years, from April 14, 2015 to April 13, 2020. All patients with a confirmed diagnosis of congenital heart disease who had undergone palliative or definitive cardiac surgery were included.&#x0D; Results: Out of the total 2698 patients, there were 1374 (50.93%) females. The total number of acyanotic congenital heart disease was 1919 (71.13%), and that of cyanotic was 779 (28.87%). Male to female ratio among acyanotic and cyanotic were 0.85:1 and 1.31:1 respectively. Among all CHDs, atrial septal defect (ASD) (38.13%) followed by ventricular septal defect (VSD) (21.68%) and atrioventricular septal defect (AVSD) (5.04%) respectively were the commonest acyanotic heart lesions. Considering only the pediatric population (age 0-18 years), the commonest was VSD (27.06%) followed by ASD (22.3%) respectively. The commonest cyanotic was tetralogy of Fallot (TOF) (14.15%) followed by double outlet right ventricle (DORV) (4.44%) and total anomalous pulmonary venous connection (TAPVC) (2.89%) respectively.&#x0D; Conclusion: Female population was slightly more in number amid acyanotic lesion whereas male population was dominant in cyanotic lesion. The commonest acyanotic CHD was ASD and, TOF was the commonest cyanotic lesion.

Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells via Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression.

NK2 homeobox 5 (Nkx2.5), a homeobox-containing transcription factor, is associated with a spectrum of congenital heart diseases. Recently, Nkx2.5 was also found to be differentially expressed in several kinds of tumors. In colorectal cancer (CRC) tissue and cells, hypermethylation of Nkx2.5 was observed. However, the roles of Nkx2.5 in CRC cells have not been fully elucidated. In the present study, we assessed the relationship between Nkx2.5 and CRC by analyzing the expression pattern of Nkx2.5 in CRC samples and the adjacent normal colonic mucosa (NCM) samples, as well as in CRC cell lines. We found higher expression of Nkx2.5 in CRC compared with NCM samples. CRC cell lines with poorer differentiation also had higher expression of Nkx2.5. Although this expression pattern makes Nkx2.5 seem like an oncogene, in vitro and in vivo tumor suppressive effects of Nkx2.5 were detected in HCT116 cells by establishing Nkx2.5-overexpressed CRC cells. However, Nkx2.5 overexpression was incapacitated in SW480 cells. To further assess the mechanism, different expression levels and mutational status of p53 were observed in HCT116 and SW480 cells. The expression of p21WAF1/CIP1, a downstream antitumor effector of p53, in CRC cells depends on both expression level and mutational status of p53. Overexpressed Nkx2.5 could elevate the expression of p21WAF1/CIP1 only in CRC cells with wild-type p53 (HCT116), rather than in CRC cells with mutated p53 (SW480). Mechanistically, Nkx2.5 could interact with p53 and increase the transcription of p21WAF1/CIP1 without affecting the expression of p53. In conclusion, our findings demonstrate that Nkx2.5 could act as a conditional tumor suppressor gene in CRC cells with respect to the mutational status of p53. The tumor suppressive effect of Nkx2.5 could be mediated by its role as a transcriptional coactivator in wild-type p53-mediated p21WAF1/CIP1 expression.

Genetic Etiology of Left-Sided Obstructive Heart Lesions: A Story in Development.

Congenital heart disease is the most common congenital defect observed in newborns. Within the spectrum of congenital heart disease are left‐sided obstructive lesions (LSOLs), which include hypoplastic left heart syndrome, aortic stenosis, bicuspid aortic valve, coarctation of the aorta, and interrupted aortic arch. These defects can arise in isolation or as a component of a defined syndrome; however, nonsyndromic defects are often observed in multiple family members and associated with high sibling recurrence risk. This clear evidence for a heritable basis has driven a lengthy search for disease‐causing variants that has uncovered both rare and common variants in genes that, when perturbed in cardiac development, can result in LSOLs. Despite advancements in genetic sequencing platforms and broadening use of exome sequencing, the currently accepted LSOL‐associated genes explain only 10% to 20% of patients. Further, the combinatorial effects of common and rare variants as a cause of LSOLs are emerging. In this review, we highlight the genes and variants associated with the different LSOLs and discuss the strengths and weaknesses of the present genetic associations. Furthermore, we discuss the research avenues needed to bridge the gaps in our current understanding of the genetic basis of nonsyndromic congenital heart disease.