The incidence of chromosome abnormalities in neonates with structural heart disease

Dykes, J.C.; Al-mousily, Mohammad F; Abuchaibe, Eda-Cristina; Silva, Jennifer N; Zadinsky, Jennifer; Duarte, Daniel; Welch, Elizabeth

doi:10.1136/heartjnl-2015-308650

Cited by 8 publications

(15 citation statements)

References 19 publications

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“…[22][23][24] The proportion of CNVs appeared slightly lower in postnatal cohorts that reported CNVs in 5-8% of neonates with CHDs. 25,26 One recent fetal cohort reported a prevalence of 16% pathogenic CNVs. 27 This proportion, however, reflects a selected population, as they only included those referred for invasive genetic testing.…”

Section: Discussionmentioning

confidence: 99%

“…The prevalence of sequence variants appeared also higher in fetuses (6.6%) than neonates, as one postnatal cohort study reported genetic syndromes in 5.1% of neonates with normal chromosomes. 26 This risk is probably higher in fetal cohorts compared to cohorts that focus exclusively on postnatal cases, as cases with TOP, intra uterine fetal demise or early neonatal death are often not included in postnatal cohorts. It is therefore important that our data are evaluated from a prenatal perspective to enable prenatal counseling at midgestation.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the large sample size and completeness of our regional CHD registry, we were able to stratify the probability of genetic diagnoses according to the specific heart defect, using not only results from karyotyping and FISH for 22q11.2, but CMA, genetic testing for specific syndromes and exome sequencing in selected cases as well. Although several recent cohorts have studied aneuploidy or 22q11.2 deletion syndrome in CHD cases, 22,23,26,29 evidence on the prevalence of other structural chromosome abnormalities and sequence variants for specific heart defects is limited. IAoA, PA-VSD and AVSD were most associated with the presence of genetic diagnoses.…”

Section: Discussionmentioning

confidence: 99%

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The prevalence of genetic diagnoses in fetuses with severe congenital heart defects

Nisselrooij

Lugthart

Clur

et al. 2020

Genetics in Medicine

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Purpose: Congenital heart defects (CHD) are associated with genetic syndromes. Rapid aneuploidy testing and chromosome microarray analysis (CMA) are standard care in fetal CHD. Many genetic syndromes remain undetected with these tests. This cohort study aims to estimate the frequency of causal genetic variants, in particular structural chromosome abnormalities and sequence variants, in fetuses with severe CHD at mid-gestation, to aid prenatal counselling. Methods: Fetuses with severe CHD were extracted from the PRECOR registry (2012-2016). We evaluated pre-and postnatal genetic testing results retrospectively to estimate the frequency of genetic diagnoses in general, as well as for specific CHDs. Results: 919 fetuses with severe CHD were identified. After exclusion of 211 cases with aneuploidy, a genetic diagnosis was found in 15.7% (111/708). These comprised copy number variants in 9.9% (70/708). In 4.5% (41/708) sequence variants were found that would have remained undetected with CMA. Interrupted aortic arch, pulmonary atresia with ventricular septal defect and atrioventricular septal defect were most commonly associated with a genetic diagnosis. Conclusion: In case of normal CMA results, parents should be offered exome sequencing sequentially, if time allows for it, especially if the CHD is accompanied by other structural malformations due to the large variety in genetic syndromes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The prevalence of genetic diagnoses in fetuses with severe congenital heart defects

Nisselrooij

Lugthart

Clur

et al. 2020

Genetics in Medicine

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“…As recruitment was center-specific, it is possible that differences in recruitment might have introduced some selection bias. For instances, the proportion of cases in the PCGC cohort with a genetic diagnosis (11%) is low compared to population-based estimates (~20%) [ 19 ]. This likely reflects the PCGC recruitment priorities (e.g., nonsyndromic over syndromic) and it is possible that some centers may have recruited a lower proportion of syndromic cases than other centers.…”

Section: Discussionmentioning

confidence: 99%

The Congenital Heart Disease Genetic Network Study: Cohort description

et al. 2018

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The Pediatric Cardiac Genomics Consortium (PCGC) designed the Congenital Heart Disease Genetic Network Study to provide phenotype and genotype data for a large congenital heart defects (CHDs) cohort. This article describes the PCGC cohort, overall and by major types of CHDs (e.g., conotruncal defects) and subtypes of conotrucal heart defects (e.g., tetralogy of Fallot) and left ventricular outflow tract obstructions (e.g., hypoplastic left heart syndrome). Cases with CHDs were recruited through ten sites, 2010–2014. Information on cases (N = 9,727) and their parents was collected through interviews and medical record abstraction. Four case characteristics, eleven parental characteristics, and thirteen parent-reported neurodevelopment outcomes were summarized using counts and frequencies and compared across CHD types and subtypes. Eleven percent of cases had a genetic diagnosis. Among cases without a genetic diagnosis, the majority had conotruncal heart defects (40%) or left ventricular outflow tract obstruction (21%). Across CHD types, there were significant differences (p<0.05) in the distribution of all four case characteristics (e.g., sex), four parental characteristics (e.g., maternal pregestational diabetes), and five neurodevelopmental outcomes (e.g., learning disabilities). Several characteristics (e.g., sex) were also significantly different across CHD subtypes. The PCGC cohort is one of the largest CHD cohorts available for the study of genetic determinants of risk and outcomes. The majority of cases do not have a genetic diagnosis. This description of the PCGC cohort, including differences across CHD types and subtypes, provides a reference work for investigators who are interested in collaborating with or using publically available resources from the PCGC.

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“…However, with the emergence of genetic technologies such as chromosomal microarray, targeted gene panels and whole exome/genome sequencing, establishing a molecular diagnosis for patients with CHD, are fast becoming a reality, even in those with sporadic forms of disease. 9,10 An important question asked by many parents at the time of diagnosis is "how and why did this happen?". 11 A lack of understanding leaves many parents with feelings of "transmission guilt," which may progress to feelings of distress and shame over their perceived wrongdoing in passing on the disease, and ultimately manifesting into depression, anxiety, and stress.…”

mentioning

confidence: 99%

“Why and how did this happen?”: development and evaluation of an information resource for parents of children with CHD

et al. 2020

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Background:The causes of CHD are complex and often unknown, leading parents to ask how and why this has happened. Genetic counselling has been shown to benefit these parents by providing information and support; however, most parents currently do not receive this service. This study aimed to develop a brochure to determine whether an information resource could improve parents’ knowledge about CHD causation and inheritance and increase psychosocial functioning.Methods:In development, the resource was assessed against several readability scales and piloted. Parents of children attending preadmission clinic for surgery were included. Assessments occurred pre- and post-receiving the information resource using a purpose-designed knowledge measure and validated psychological measures.Results:Participant’s (n = 52) knowledge scores increased significantly from the pre-questionnaire ( ${\overline x}\, = \,5/10$ , sd = 2.086) to post-questionnaire ( $\overline x\, = \,7.88/10$ , sd = 2.094, p < 0.001), with all aware that CHD can be caused by genetic factors after reading the brochure. Perceived personal control also increased from pre- ( $\overline x\, = \,11.856/18$ , sd = 4.339) to post-brochure ( $\overline x\, = \,14.644/18$ , sd = 3.733, p < 0.001), and many reported reduced feelings of guilt. No negative emotional response to the brochure was reported. The information provided was considered relevant (88%), reassuring (86%), and 88% would recommend the brochure to other parents. However, some wanted more emotional support and assistance in what to tell their child.Conclusions:Use of the information resource significantly enhanced parents’ knowledge of CHD causation and increased their psychosocial functioning. It is a valuable resource in the absence of genetic counselling; however, it should not replace formal genetic counselling when required.

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The incidence of chromosome abnormalities in neonates with structural heart disease

Abstract: Chromosome abnormalities, including syndromes, are prevalent in newborns with congenital heart disease. Further research is needed to evaluate the utility of cytogenetic screening in all children with congenital heart disease.

Cited by 8 publications

References 19 publications

The prevalence of genetic diagnoses in fetuses with severe congenital heart defects

The prevalence of genetic diagnoses in fetuses with severe congenital heart defects

The Congenital Heart Disease Genetic Network Study: Cohort description

“Why and how did this happen?”: development and evaluation of an information resource for parents of children with CHD

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