Adolescents with congenital heart defects: a patient and parental perspective of genetic information and genetic risk.
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ABSTRACT:
SUBMITTER: Crawford CA
PROVIDER: S-EPMC8444052 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The etiology for the majority of congenital heart defects (CHD) is unknown. We identified a patient with unbalanced atrioventricular septal defect (AVSD) and hypoplastic left ventricle who harbored an ~0.3 Mb monoallelic deletion on chromosome 3p14.1. The deletion encompassed the first four exons of FOXP1, a gene critical for normal heart development that represses cardiomyocyte proliferation and expression of Nkx2.5. To determine whether FOXP1 mutations are found in patients with CHD, we sequenced FOXP1 in 82 patients with AVSD or hypoplastic left heart syndrome. We discovered two patients who harbored a heterozygous c.1702C>T variant in FOXP1 that predicted a potentially deleterious substitution of a highly conserved proline (p.Pro568Ser). This variant was not found in 287 controls but is present in dbSNP at a 0.2% frequency. The orthologous murine Foxp1 p.Pro596Ser mutant protein displayed deficits in luciferase reporter assays and resulted in increased proliferation and Nkx2.5 expression in cardiomyoblasts. Our data suggest that haploinsufficiency of FOXP1 is associated with human CHD.
| S-EPMC5717756 | biostudies-literature
Project description:Structural birth defects in the kidney and urinary tract are observed in 0.5% of live births and are a major cause of end-stage renal disease, but their genetic aetiology is not well understood. Here we analyse 135 lines of mice identified in large-scale mouse mutagenesis screen and show that 29% of mutations causing congenital heart disease (CHD) also cause renal anomalies. The renal anomalies included duplex and multiplex kidneys, renal agenesis, hydronephrosis and cystic kidney disease. To assess the clinical relevance of these findings, we examined patients with CHD and observed a 30% co-occurrence of renal anomalies of a similar spectrum. Together, these findings demonstrate a common shared genetic aetiology for CHD and renal anomalies, indicating that CHD patients are at increased risk for complications from renal anomalies. This collection of mutant mouse models provides a resource for further studies to elucidate the developmental link between renal anomalies and CHD.
| S-EPMC4804176 | biostudies-literature
Project description:Congenital conotruncal heart defects (CCHD) are a subset of serious congenital heart defects (CHD) of the cardiac outflow tracts or great arteries. Its frequency is estimated in 1/1000 live births, accounting for approximately 10⁻30% of all CHD cases. Chromosomal abnormalities and copy number variants (CNVs) contribute to the disease risk in patients with syndromic and/or non-syndromic forms. Although largely studied in several populations, their frequencies are barely reported for Latin American countries. The aim of this study was to analyze chromosomal abnormalities, 22q11 deletions, and other genomic imbalances in a group of Argentinean patients with CCHD of unknown etiology. A cohort of 219 patients with isolated CCHD or associated with other major anomalies were referred from different provinces of Argentina. Cytogenetic studies, Multiplex-Ligation-Probe-Amplification (MLPA) and fluorescent in situ hybridization (FISH) analysis were performed. No cytogenetic abnormalities were found. 22q11 deletion was found in 23.5% of the patients from our cohort, 66% only had CHD with no other major anomalies. None of the patients with transposition of the great vessels (TGV) carried the 22q11 deletion. Other 4 clinically relevant CNVs were also observed: a distal low copy repeat (LCR)D-E 22q11 duplication, and 17p13.3, 4q35 and TBX1 deletions. In summary, 25.8% of CCHD patients presented imbalances associated with the disease.
| S-EPMC6162499 | biostudies-literature
Project description:In this article, patient activity in 8 audio recorded specialist consultations on fetal cardiology is investigated in order to explore how, why and when patients tend to participate in encounters in which the doctor dominates the interaction. The overall question is: How can the participation of patients in the consultations be connected to the development of higher levels of health literacy, i.e. to interactive literacy and to critical literacy? Patient participation is here understood as interactive action and is analyzed in terms of different interactive moves, which are related to different recurring topics. Despite the highly standardized format of the consultations, there is a large variation between the patients' participation: between 0.7 and 2.8 moves per minute. The patients participate most during the topics 'Prevalence' and 'Consultations' and least during the topic 'The normal heart'. Although most of the patients' moves are responses to what the doctor says, they remarkably often pose questions and use so called rejoinders. By posing questions, they take control of the information flow and sometimes even change the topics. By using rejoinders, they analyze the problems involved in the discussion e.g. by asking for clarifications or confirmation. Patients with a low over-all participation rate also use fewer moves that indicate higher literacy levels. The qualitative analysis problematizes the idea of a simple scale from basic literacy to critical literacy. Moves that indicate basic literacy skills are interactively important for the learning activity, led by the doctor. However, patients who mainly support the doctor's initiatives don't take the opportunity to influence the flow of information in ways that might favor their health literacy development.
| S-EPMC6655745 | biostudies-literature
Project description:BackgroundImproved treatment of congenital heart defects (CHDs) has increased survival of persons with CHDs; however, no U.S. population-based systems exist to assess prevalence, healthcare utilization, or longer-term outcomes among adolescents and adults with CHDs.MethodsNovel approaches identified individuals aged 11-64 years who received healthcare with ICD-9-CM codes for CHDs at three sites: Emory University in Atlanta, Georgia (EU), Massachusetts Department of Public Health (MA), New York State Department of Health (NY) between January 1, 2008 (2009 for MA) and December 31, 2010. Case-finding sources included outpatient clinics; Medicaid and other claims data; and hospital inpatient, outpatient, and emergency visit data. Supplemental information came from state vital records (EU, MA), and birth defects registries (EU, NY). Demographics and diagnostic and procedural codes were linked, de-duplicated, and shared in a de-identified dataset. Cases were categorized into one of five mutually exclusive CHD severity groups; non-cardiac comorbidity codes were grouped into broad categories.Results73,112 individuals with CHD codes in healthcare encounters were identified. Primary data source type varied: clinics (EU, NY for adolescents), claims (MA), hospital (NY for adults). There was a high rate of missing data for some variables and data varied in format and quality. Some diagnostic codes had poor specificity for CHD ascertainment.ConclusionsTo our knowledge, this is the first population-based, multi-site CHD surveillance among adolescents and adults in the U.S. Identification of people living with CHDs through healthcare encounters using multiple data sources was feasible, though data quality varied and linkage/de-duplication was labor-intensive.
| S-EPMC6701175 | biostudies-literature
Project description:BackgroundMost non-syndromic congenital heart defects (CHD) are caused by a complex interaction between maternal lifestyle factors, environmental exposures, and maternal and fetal genetic variants. Maternal periconceptional intake of folic acid containing vitamin supplements is reported to decrease the risk of CHD. The 677C-->T and 1298A-->C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene decrease enzyme activity.ObjectiveTo examine the relation between CHD and maternal and fetal MTHFR polymorphisms.Methods375 nuclear families were studied. The transmission/disequilibrium test was used to test for transmission distortion in complete triads. A log-linear approach was used to test for associations between CHD and maternal and offspring polymorphisms, and to estimate independently the contributions of maternal and fetal variants to relative risks. Haplotype frequencies were estimated and a haplotype transmission disequilibrium test carried out.ResultsThe 1298C allele was transmitted less often than expected (p = 0.0013). There was no distortion in the transmission of the 677T allele, neither was there evidence of a parent of origin effect in the transmission of either of the single nucleotide polymorphisms. The 677C-1298C haplotype was also transmitted less often than expected (p = 0.0020). The relative risk associated with inheriting one copy of the 1298C allele was 0.64 (95% confidence interval, 0.48 to 0.87) and the that associated with inheriting two copies of the 1298C allele, 0.38 (0.21 to 0.70).ConclusionsThe apparent protective effect of the MTHFR 1298C allele against CHD could have several explanations and further study is needed.
| S-EPMC2564637 | biostudies-literature
Project description:BackgroundCongenital heart defect (CHD) is the leading cause of birth defects globally, which results in a great disease burden. It is still imperative to detect the risk factors of CHD. This umbrella review aimed to comprehensively summarize the evidence and grade the evidence of the associations between non-genetic risk factors and CHD.MethodsDatabases including Medline, Embase, Web of Science, Cochrane Library, and four Chinese databases were searched from inception to 18 Jan 2022. The reference lists of systematic reviews (SR) and meta-analyses (MA) were screened, which aimed to explore the non-genetic risk factors of CHD. Subsequently, titles and abstracts of identified records and full texts of selected SR/MA were screened by two independent reviewers based on predefined eligibility criteria. A priori developed extraction form was used to abstract relative data following the PRISMA 2020 and MOOSE guidelines. The risk of bias was assessed with the AMSTAR2 instrument. Data were synthesized using fixed-effects and random-effects meta-analyses, respectively. Finally, the evidence on the association of non-genetic risk factors and CHD was graded using Ioannidis's five-class evidence grade.ResultsA total of 56 SRs, encompassing 369 MAs, were identified. The risk factors included relative factors on air pollution, reproductive-related factors, parental age and BMI, parental life habits, working and dwelling environment, maternal drug exposure, and maternal disease. Based on AMSTAR2 criteria, only 16% (9/56) of SRs were classified as "Moderate". One hundred and two traceable positive association MAs involving 949 component individual studies were included in further analysis and grading of evidence. Family genetic history, number of abortions, maternal obesity, especially moderate or severe obesity, decoration materials, harmful chemicals, noise during pregnancy, folic acid supplementation, SSRIs, SNRIs, any antidepressants in the first trimester, maternal DM (including both PGDM and GDM), and gestational hypertension were convincing and highly suggestive factors for CHD. After sensitivity analyses based on cohort studies, some grades of evidence changed.ConclusionThe present umbrella review will provide evidence-based information for women of childbearing age before or during pregnancy to prevent CHD. In addition, sensitivity analysis based on cohort studies showed the changed evidence levels. Therefore, future SR/MA should concern the sensitivity analysis based on prospective birth cohort studies and case-control studies.
| S-EPMC9055777 | biostudies-literature
Project description:BackgroundWhen a heart defect is prenatally diagnosed in the fetus, expectant parents experience a great need for information about various topics. After the diagnosis, the Web is used for supplemental information, and the scarcity of research calls attention to the need to explore patient information websites from the perspectives of the intended consumers.ObjectiveThe overarching aim of this study was to explore the quality of Swedish patient information websites about congenital heart defects, from the perspectives of individuals with experience of a prenatal diagnosis of congenital heart defect in the fetus.MethodsThis was a mixed-methods study of websites identified through systematic searches in the two most used Web-based search engines. Of the total 80 screened hits, 10 hits led to patient information websites about congenital heart defects. A quality assessment tool inspired by a previous study was used to evaluate each website's appearance, details, relevance, suitability, information about treatment choices, and overall quality. Answers were given on a 5-point Likert scale, ranging from 1, representing the lowest score, to 5, representing the highest score. Each website was assessed individually by persons with experience of continued (n=4) and terminated (n=5) pregnancy following a prenatal diagnosis. Assessments were analyzed with Kendall's coefficient of concordance W, Mann-Whitney U test, Friedman's test, and a Wilcoxon-Nemenyi-McDonald-Thompson test. In addition, each assessor submitted written responses to open-ended questions in the quality assessment tool, and two joint focus group discussions were conducted with each group of assessors. The qualitative data were analyzed with inductive manifest content analysis.ResultsAssessments represented a low score (median=2.0) for treatment choices and moderate scores (median=3.0) for appearance, details, relevance, suitability, and overall quality. No website had a median of the highest achievable score for any of the questions in the quality assessment tool. Medians of the lowest achievable score were found in questions about treatment choices (n=4 websites), details (n=2 websites), suitability (n=1 website), and overall quality (n=1 website). Websites had significantly different scores for appearance (P=.01), details (P<.001), relevance (P<.001), suitability (P<.001), treatment choices (P=.04), and overall quality (P<.001). The content analysis of the qualitative data generated six categories: (1) advertisements, (2) comprehensiveness, (3) design, (4) illustrations and pictures, (5) language, and (6) trustworthiness. Various issues with the included websites were highlighted, including the use of inappropriate advertisements, biased information, poor illustrations, complex language, and poor trustworthiness.ConclusionsFrom the perspectives of the intended consumers, patient information websites about congenital heart defects are, to a large extent, inadequate tools for supplemental information following a prenatal diagnosis. Health professionals should initiate discussions with patients about their intentions to use the Web, inform them about the varied quality in the Web-based landscape, and offer recommendations for appropriate Web-based sources.
| S-EPMC5615220 | biostudies-literature
Project description:To compare patient-reported, health-related quality of life (QoL) for children with serious congenital heart defects (CHDs) and unaffected classmates and to investigate the demographic and clinical factors influencing QoL.Retrospective cohort study.UK National Health Service.UK-wide cohort of children with serious CHDs aged 10-14 years requiring cardiac intervention in the first year of life in one of 17 UK paediatric cardiac surgical centres operating during 1992-1995. A comparison group of classmates of similar age and sex was recruited.Child self-report of health-related QoL scores (Pediatric Quality of Life Inventory, PedsQL) and parental report of schooling and social activities.Questionnaires were completed by 477 children with CHDs (56% boys; mean age 12.1 (SD 1.0) years) and 464 classmates (55%; 12.0 (SD 1.1) years). Children with CHDs rated QoL significantly lower than classmates (CHDs: median 78.3 (IQR 65.0-88.6); classmates: 88.0 (80.2-94.6)) and scored lower on physical (CHDs: 84.4; classmates: 93.8; difference 9.4 (7.8 to 10.9)) and psychosocial functioning subscales (CHDs: 76.7, classmates: 85.0; difference 8.3 (6.0 to 10.6)). Cardiac interventions, school absence, regular medications and non-cardiac comorbidities were independently associated with reduced QoL. Participation in sport positively influenced QoL and was associated with higher psychosocial functioning scores.Children with serious CHDs experience lower QoL than unaffected classmates. This appears related to the burden of clinical intervention rather than underlying cardiac diagnosis. Participation in sports activities is positively associated with increased emotional well-being. Child self-report measures of QoL would be a valuable addition to clinical outcome audit in this age group.
| S-EPMC3995241 | biostudies-literature
Project description:Clinical genetic testing for specific isolated congenital heart defects (CHD) is becoming standard of care in pediatric cardiology practice. Both genetic knowledge and attitudes toward genetic testing are associated with an increased utilization of genetic testing, but these factors have not been evaluated in parents of children with CHD. We mailed a survey to measure the demographics, genetic knowledge, and attitudes towards genetic testing of parents of children with CHD who previously consented to participate in a separate research study of the genetic etiology of left ventricular outflow tract malformations (LVOT). Of the 378 eligible families, 190 (50%) returned surveys with both parents completing surveys in 97 (51%) families, resulting in 287 participants. Genetic knowledge was assessed on an adapted measure on which the mean percent correct was 73.8%. Educational attainment and household income were directly and significantly associated with genetic knowledge (P?<?0.001). Attitudes about the health effects of genetic testing were favorable with at least 57% agreeing that genetic testing would be used for managing health care and finding cures for disease. Conversely, a minority of participants found it likely that genetic testing would be used for insurance (up to 39.9%), employment (15.8%), or racial/social discrimination (up to 11.2%). Parents of younger children were less likely to endorse employment or racial/social discrimination. Genetic knowledge was not correlated with specific attitudes. Among parents of children with CHD, genetic knowledge was directly associated with household income and education, but additional research is necessary to determine what factors influence attitudes towards genetic testing.
| S-EPMC4236279 | biostudies-literature