scholarly journals The fitness cost of a congenital heart defect shapes its genetic architecture

2019 ◽  
Author(s):  
Ehiole Akhirome ◽  
Suk D. Regmi ◽  
Rachel A. Magnan ◽  
Nelson Ugwu ◽  
Yidan Qin ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart Defect ◽  
Genetic Architecture ◽  
Congenital Heart ◽  
Septal Defect ◽  
Heart Defects ◽  
Atrioventricular Septal Defect ◽  
Fitness Cost ◽  
Heart Defect

ABSTRACTBackgroundIn newborns, severe congenital heart defects are rarer than mild ones. The reason why is unknown, but presumably related to a liability threshold that rises with the severity of a defect. Because the same genetic mutation can cause different defects, other variables may contribute to pushing an individual past a defect-specific liability threshold. We consider here how variables in the genetic architecture of a heart defect depend upon its fitness cost, as defined by the likelihood of survival to reproductive age in natural history studies.MethodsWe phenotyped ~10,000 Nkx2-5+/- newborn mice, a model of human congenital heart disease, from two inbred strain crosses. Genome-wide association analyses detected loci that modify the risk of an atrial septal defect, membranous or muscular ventricular septal defect, or atrioventricular septal defect. The number of loci, heritability and quantitative effects on risk of pairwise (G×GNkx) and higher-order (G×G×GNkx) epistasis between the loci and Nkx2-5 mutation were examined as a function of the fitness cost of a defect.ResultsNkx2-5+/- mice have pleiotropic heart defects; about 70% have normal hearts. The model recapitulates the epidemiological relationship between the severity and incidence of a heart defect. Neither the number of modifier loci nor heritability depends upon the severity of a defect, but G×GNkx and G×G×GNkx effects on risk do. Interestingly, G×G×GNkx effects are three times more likely to suppress risk when the genotypes at the first two loci are homozygous and from the same, rather than opposite strains in a cross. Syn- and anti-homozygous genotypes at G×G×GNkx interactions can have an especially large impact on the risk of an atrioventricular septal defect.ConclusionsGiven a modestly penetrant mutation, epistasis contributes more to the risk of severe than mild congenital heart defect. Conversely, genetic compatibility between interacting genes, as indicated by the protective effects of syn-homozygosity at G×G×GNkx interactions, plays a newfound role in the robustness of cardiac development. The experimental model offers practical insights into the nature of genetic risk in congenital heart disease. The results more fundamentally address a longstanding question regarding how mutational robustness could arise from natural selection.

scholarly journals Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service

2014 ◽  
Vol 32 (2) ◽  
pp. 159-163 ◽  
Author(s):  
Felipe Alves Mourato ◽  
Lúcia Roberta R. Villachan ◽  
Sandra da Silva Mattos
Keyword(s):  
Congenital Heart Disease ◽  
Pulmonary Hypertension ◽  
Down Syndrome ◽  
Heart Disease ◽  
Congenital Heart ◽  
Septal Defect ◽  
Heart Diseases ◽  
Heart Defects ◽  
Descriptive Analysis ◽  
Atrioventricular Septal Defect

OBJECTIVE:To determine the frequence and profile of congenital heart defects in Down syndrome patients referred to a pediatric cardiologic center, considering the age of referral, gender, type of heart disease diagnosed by transthoracic echocardiography and its association with pulmonary hypertension at the initial diagnosis.METHODS:Cross-sectional study with retrospective data collection of 138 patients with Down syndrome from a total of 17,873 records. Descriptive analysis of the data was performed, using Epi-Info version 7.RESULTS: Among the 138 patients with Down syndrome, females prevailed (56.1%) and 112 (81.2%) were diagnosed with congenital heart disease. The most common lesion was ostium secundum atrial septal defect, present in 51.8%, followed by atrioventricular septal defect, in 46.4%. Ventricular septal defects were present in 27.7%, while tetralogy of Fallot represented 6.3% of the cases. Other cardiac malformations corresponded to 12.5%. Pulmonary hypertension was associated with 37.5% of the heart diseases. Only 35.5% of the patients were referred before six months of age.CONCLUSIONS: The low percentage of referral until six months of age highlights the need for a better tracking of patients with Down syndrome in the context of congenital heart disease, due to the high frequency and progression of pulmonary hypertension.

scholarly journals Pattern of congenital heart diseases among clinically diagnosed Down’s syndrome children

2015 ◽  
Vol 6 (1) ◽  
pp. 18-20
Author(s):  
Abu Sayed Munsi ◽  
Manzoor Hussain ◽  
Rezoana Rima ◽  
Robi Biswas ◽  
Salahuddin Mahmud ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Septal Defect ◽  
Heart Defects ◽  
Ductus Arteriosus ◽  
Atrioventricular Septal Defect ◽  
Female Ratio ◽  
Cardiology Department

Background : Down’s syndrome (DS) is the commonest genetic cause of malformation with congenital heart defects.Objectives : This study was conducted to evaluate the frequency of various congenital heart defects in children with clinically diagnosed Down’s syndrome in Dhaka Shishu Hospital.Material & Methods : This prospective study was conducted at Pediatric cardiology department of Dhaka Shishu Hospital from 1st February 2013 to 31st January 2014. Admitted Seventy four phenotypically Down’s syndrome patients were included in this study. After taking detailed history and physical examination, all these patients were subjected to Color Doppler echocardiography in addition to routine laboratory investigations.Results : Total 74 down’s Syndrome patients were admitted at cardiology department during the study period. Among them 35 (47.29%) were males and 39 (52.71%)were females with male to female ratio of 1:1.12. Atrioventricular septal defect was the commonest defect 15(20.27%), followed by Ventricular septal defect 12(16.21%), Patent ductus arteriosus 11(14.86%), Atrial septal defect 7(9.46%), Tetralogy of Fallots 3(4.05%), Pentology of Fallots 2(2.70%), Dextrocardia with D _ TGA 1(1.35%), Total anomalous pulmonary venous drainage 1(1.35%) but Multiple congenital heart disease were 22(29.72%) cases. Along with congenital heart disease 3(4.05%) patients had GIT abnormality, 4(5.4%) patient had congenital hypothyroidism and 3(4.05%) patients had Eye problem.Conclusion : Congenital heart defects are common in children with Down’s syndrome. The commonest one is Atrioventricular septal defect in our set-up.Northern International Medical College Journal Vol.6(1) 2014: 18-20

scholarly journals Pattern and frequency of pediatric congenital heart disease at the Cardiac Research Institute of Kabul Medical University, Afghanistan

2018 ◽  
Vol 58 (3) ◽  
pp. 106-9
Author(s):  
Abdul Muhib Sharifi
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Atrial Septal Defect ◽  
Tetralogy Of Fallot ◽  
Congenital Heart ◽  
Septal Defect ◽  
Heart Defects ◽  
Cardiac Lesions ◽  
Medical University ◽  
Research Institute

Background Congenital heart disease (CHD) is the most common birth defect, with incidence of 0.7-0.9 live birth; it increases to 2-6% if first degree relative is affected. In Afghanistan majority of births take place at home and routine screening of neonates is not common, so true birth prevalence of CHD cannot be possibly calculated. Therefore, true prevalence of CHD in our population is unknown. Objective To verify the current pattern and frequency distribution of congenital heart disease (CHD) at the Cardiac Research Institute of Kabul Medical University. Methods  This retrospective study was conducted in children aged 0-14 years, who underwent echocardiography for possible congenital heart disease from January 2015 to December 2016. Results  Of 560 patients who underwent echocardiography, 392(70%) had cardiac lesions. Congenital cardiac lesions were found in 235 (60% of those with lesions) patients, while 157 (40%) patients had rheumatic heart disease. Patients with CHD were further subdivided into acyanotic and cyanotic groups. The majority of acyanotic group had isolated atrial septal defect (55%) while the most common lesion in the cyanotic group was Tetralogy of Fallot (42%). Conclusion Congenital heart defects are the most common heart disease in the pediatric population presenting at the Cardiac Research Institute of Kabul Medical University. Atrial septal defect (ASD) was the most common acyanotic defect, while Tetralogy of Fallot (ToF) is the most common cyanotic defect.

Status and Challenges of Care in Africa for Adults With Congenital Heart Defects

2017 ◽  
Vol 8 (4) ◽  
pp. 495-501 ◽  
Author(s):  
Frank Edwin ◽  
Liesl Zühlke ◽  
Heba Farouk ◽  
Ana Olga Mocumbi ◽  
Kow Entsua-Mensah ◽  
...  
Keyword(s):  
Health Care ◽  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart Defect ◽  
Congenital Heart ◽  
Heart Defects ◽  
Health Care Systems ◽  
Birth Prevalence ◽  
Care Systems ◽  
Courageous Action

The 54 countries in Africa have an estimated total annual congenital heart defect (CHD) birth prevalence of 300,486 cases. More than half (51.4%) of the continental birth prevalence occurs in only seven countries. Congenital heart disease remains primarily a pediatric health issue in Africa because of the deficient health-care systems: the adults with CHD made up just 10% of patients with CHD in Ghana, and 13.7% of patients with CHD presenting for surgery in Mozambique. With Africa’s population projected to double in the next 35 years, the already deficient health systems for CHD care will suffer unbearable strain unless determined and courageous action is undertaken by the African leaders.

scholarly journals Implantable cardioverter defibrillators in adult congenital heart disease: long-term follow up of therapies, complications and clinical events

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
V Ferreira ◽  
M Cruz Coutinho ◽  
G Portugal ◽  
P Silva Cunha ◽  
B Valente ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Primary Prevention ◽  
Congenital Heart ◽  
Septal Defect ◽  
Long Term Outcomes ◽  
Icd Implantation ◽  
Heart Defect

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Adults with congenital heart disease (ACHD) at increased risk for sudden cardiac death (SCD) often undergo implantable cardioverter defibrillator (ICD) implantation at young ages. Data evaluating the long-term outcomes of ICD in this population remain scarce. We aimed to characterize the population with ACHD and an ICD. Methods Consecutive ACHD submitted to an ICD implantation in a single tertiary center were evaluated. Data on baseline clinical features, heart defect, indication for ICD, type of device, ICD-related complication and therapies and mortality during follow-up were collected. Results A total of 34 patients (P) were evaluated. Median age at implant was 39.3 years (interquartile range [IQR] 29-5-53.6) and median left ventricular ejection fraction (LVEF) was 43.5% (IQR 28.0-53.3). The most common heart defect was tetralogy of Fallot (11P;32,3%), followed by dextro-transposition of the great arteries, ostium secundum atrial septal defect (ASD) and ventricular septal defect (Figure 1). All P were submitted to surgical correction (median age at surgery 12.5 years [IQR 3.0-29.1]). Sixteen P underwent ICD implantation for primary prevention of SCD, owing to complex cardiopathy and ventricular dysfunction, and 18P due to spontaneous ventricular tachyarrhythmias. The implantable devices were a single-chamber ICD in 55.9%, a double-chamber ICD in 17.6%, a subcutaneous ICD in 20.6% and a CRT-D in 5.9%. During a median follow-up of 4.5 years (IQR 2.1-8.8), 52.9% of the P received appropriate ICD therapies, corresponding to 37.5% and 66.7% of primary and secondary prevention P, respectively. Median time to first arrhythmic event was 25.3 months (IQR 13.7-52.9). Six P (17.6%) suffered ICD-related complications and 20.6% received inappropriate therapies due to supraventricular tachyarrhythmias. During follow-up, 8.8% were submitted to heart transplant and 29.4% died (Table 1).  ICD therapies were associated with a composite of death, cardiac transplantation and hospital admission (OR 5.0, 95% CI 1.0-24.3). Conclusion ACHD with ICD experience high rate of appropriate therapies, including those implanted for primary prevention. The long-term burden of ICD-related complications and inappropriate shocks underlines the need for careful risk stratification and close monitoring. The increased survival of this population justifies collecting data on long-term outcomes to improve its care. Abstract Figure.

scholarly journals PREVALENCE OF CONGENITAL HEART DISEASE IN UMERKOT

2021 ◽  
Vol 70 (Suppl-4) ◽  
pp. S824-27
Author(s):  
Mohsin Saif ◽  
Abdul Fatah ◽  
Waqas Akhtar ◽  
Farah Javed ◽  
Ali Mujtaba Tahir ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Ventricular Septal Defect ◽  
Tetralogy Of Fallot ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Septal Defect ◽  
Heart Defects ◽  
Cross Sectional ◽  
Male Preponderance

Objective: To study the prevalence and the pattern of distribution of congenital heart disease.Study Design: Descriptive cross-sectional study.Place and Duration of Study: The study was conducted at outpatient department (OPD) of CMH Chhor and DHQ Umerkot, Sindh (Pakistan), from Dec 2019 to Mar 2020.Methodology: All the children (<12 years age) presenting to Paediatric OPD of the two hospitals were enrolled into study. Any patient with either a history or clinical examination pointing towards a suspected congenital heart disease was referred to Paediatric Cardiologist for 2-D echocardiogram. Details of the patient were recorded on designated proforma. Results: A total of 273 patients were diagnosed with congenital heart disease. Out of these, 114 (41.7%) were female and 159 (58.2%) were male (male: female of 1.4:1). The age of the children was ranging from 2 months to 12 years, 153 (56.04%) had simple heart defects, while 120 (43.9%) had complex or multiple congenital heart anomalies. Amongst the 273 patients, 25.3% were cyanotic and 74.7% had acyanotic heart disease. Most common lesion identified was ventricular septal defect (29.6%), followed by Tetralogy of Fallot in 20.8%. Conclusion: Acyanotic heart defects confirms to the major bulk of congenital heart defects with male preponderance.

scholarly journals DOWN’S SYNDROME;

2013 ◽  
Vol 20 (06) ◽  
pp. 898-903
Author(s):  
SHAKIL AHMAD ◽  
IMRAN SARWAR ◽  
NISAR KHAN SAJID
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Maternal Age ◽  
Congenital Heart ◽  
Septal Defect ◽  
Heart Defects ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Septal Defects ◽  
Age At Birth

Objective: To evaluate the various types of congenital heart defects and to determine their frequency in children withDown’s syndrome. Study Design: Descriptive study. Place and duration of study: Department of Pediatrics, Independent UniversityHospital Faisal Abad Pakistan, from January 2010 to December 2012. Methodology: 93 children between the ages of day 1 to 12 years,diagnosed clinically as Down’s syndrome based on its characteristic phenotypic appearance, were included in the study. A detailedhistory, physical examination and evaluation of cardiovascular status (including Chest x-ray, Electrocardiogram and Echocardiography)were performed in each Down’s syndrome case. Variables of interest included age, sex, maternal age at birth and type and frequency ofcongenital heart disease. Results: Congenital heart disease was present in 48 (51.62%) children out of 93 children with Down’ssyndrome. Congenital cardiac defects in order of predominant type and their frequency included Ventricular septal defect (29, 60.4%),Atrioventricular septal defect (14, 29.1%), Atrial septal defect (2, 4.1%), Patent ductus arteriosis (2, 4.1%) and Tetralogy of Fallots (1,2%). 68 (73.2%) Down’s syndrome children (n=93) presented during their first year of life with mean age of 7±4 months. Malepredominance was observed in both with and without congenital heart disease Down’s syndrome children (male: female 1.7:1 and 2.5:1respectively). Mean maternal age at birth was 27±2 years. Conclusions: Congenital heart disease (CHD) is frequently associated withDown’s syndrome (DS). Ventricular septal defects and atrioventricular septal defects are the most common forms of CHDs in DS childrenof our region. Their earlier presentation (in infancy) and significant contribution to the morbidity and mortality of DS children warrantsearly diagnosis of DS and mandatory screening of all DS children for associated CHDs.

scholarly journals Down Syndrome and Congenital Heart Disease: Single centre, Prospective Study

2013 ◽  
Vol 2 (2) ◽  
pp. 96-101 ◽  
Author(s):  
Maniah Shrestha ◽  
U Shrestha
Keyword(s):  
Congenital Heart Disease ◽  
Pulmonary Hypertension ◽  
Down Syndrome ◽  
Heart Disease ◽  
Prospective Study ◽  
Congenital Heart ◽  
Septal Defect ◽  
Ductus Arteriosus ◽  
Atrioventricular Septal Defect ◽  
Children With Down Syndrome

Background: The objective of this study was to evaluate the children with down syndrome regarding the frequency and types of congenital heart disease and associated pulmonary hypertension. Method: A prospective study was carried out to all the children with down syndrome visited in pediatric outpatient department over the period of one year. Necessary data were recorded in preformed format. Results: Fifty children with down syndrome were evaluated. Forty (80%) had an associated congenital heart disease. The median age at diagnosis was 2 years (range = 4 days to 12 years). In 26 patients (65%), the cardiac lesion was isolated, while 14 patients (35%) had multiple defects. The most common single defect was ventricular septal defect (VSD), found in 9 of the 40 patients (22.5%), followed by atrioventricular septal defect (AVSD) in 15%, atrial septal defect (ASD) and patent ductus arteriosus (PDA) each in 10%. The most frequent concomitant malformation found co-existing with other congenital cardiac lesions was PDA (15%). Pulmonary hypertension was found in 21 of 40 patients (52.5%) and AVSD was most frequently associated with pulmonary hypertension. Conclusion: Congenital heart disease is very common in patient with down syndrome. VSD is the most common cardiac defect and AVSD is second to VSD. Patient with down syndrome with CHD frequently develop pulmonary hypertension at younger age hence early cardiac screening by echocardiography in these patients is crucial. Early diagnosis and management is the key to avoid irreversible hemodynamic consequences of the defect. Nepal Journal of Medical Sciences | Volume 02 | Number 02 | July-December 2013 | Page 96-101 DOI: http://dx.doi.org/10.3126/njms.v2i2.8944

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