<scp>COngenital</scp> heart disease and the Diagnostic yield with Exome sequencing (<scp>CODE</scp>) study: prospective cohort study and systematic review

Mone, Fionnuala; Eberhardt, Ruth Y; Morris, R.; Hurles, Matthew E.; McMullan, DJ; Maher, Eamonn R.; Lord, Jenny; Chitty, Lyn S.; Giordano, Jessica L.; Wapner, Ronald J.; Kilby, Mark D.

doi:10.1002/uog.22072

Cited by 66 publications

(49 citation statements)

References 45 publications

(156 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may have underestimated the prevalence of chromosomal aberrations as exome sequencing (ES) was not performed. A recent study and meta‐analysis by Mone et al found a diagnostic yield of ES in isolated CHD was 11.5%, 20 however, whether this applies to isolated VSDs, in particular, is unknown.…”

Section: Discussionmentioning

confidence: 99%

Prenatally detected isolated ventricular septum defects and the association with chromosomal aberrations—A nationwide register‐based study from Denmark

et al. 2020

View full text Add to dashboard Cite

Objective To evaluate the association between prenatally detected isolated ventricular septum defects (VSDs) and chromosomal aberrations in a nationwide study in Denmark. Method Nationwide, register‐based study with prospectively collected data including all singleton pregnancies from 2014‐2018. From the Danish Fetal Medicine Database, we retrieved data on maternal characteristics, first‐trimester biomarkers, pre‐ and postnatal diagnoses, genetic test results, and pregnancy outcomes. VSDs were considered isolated in the absence of other malformations or soft markers, and with a low first‐trimester risk assessment for trisomies 21, 18 and 13. All cases of an isolated VSD with a chromosomal anomaly were audited. The genetic tests included karyotyping and chromosomal microarray. Results We retrieved data on 292 108 singleton pregnancies; 323 registered with a prenatally detected VSD and 697 with a VSD detected postnatally (incidence of 0.35%). Only 1/153 (0.7%, 95% CI 0.02;3.6%) of the isolated prenatally detected VSDs had an abnormal genetic test result (del (8)(q23.1)). Moreover, they had a lower free β‐hCG MoM (0.9 MoM vs 0.99 MoM, P = 0.02), and were more likely born small for gestational age (SGA), defined as birthweight 2 or more SD below the mean, compared with the control population (5.2% vs 2.5%, P = 0.03). Conclusion We found a prevalence of chromosomal aberrations of 0.7% in fetuses with a prenatally detected isolated VSD. Moreover, we found an association between isolated VSDs and a larger proportion being born SGA.

show abstract

Section: Discussionmentioning

confidence: 99%

Prenatally detected isolated ventricular septum defects and the association with chromosomal aberrations—A nationwide register‐based study from Denmark

et al. 2020

View full text Add to dashboard Cite

show abstract

“…A recent study performed in UK fetal medicine centers identified that the diagnostic yield of prenatally diagnosed CHD using quantitative fluorescence-PCR (QF-PCR), chromosome microarray (CMA), and exome sequencing (ES) was 15.6%, 13.7%, and 10.2%, respectively [ 31 ]. Another recent study concluded that most CHD diagnoses using prenatal ES are associated with extracardiac anomalies rather than isolated cardiac abnormalities [ 32 ]. Therefore, genetic testing has a low yield for sporadic CHD but should be used in patients with familial and syndromic CHD, despite the existence of a significant proportion of incidental findings and variants of unknown significance.…”

Section: Genetic Basismentioning

confidence: 99%

Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Diz

Toro

César

et al. 2021

JPM

View full text Add to dashboard Cite

Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malformations overall after malformations of the central nervous system. The severity of different types of congenital heart disease varies depending on the combination of associated anatomical defects. The causes of these malformations are usually considered multifactorial, but genetic variants play a key role. Currently, use of high-throughput genetic technologies allows identification of pathogenic aneuploidies, deletions/duplications of large segments, as well as rare single nucleotide variants. The high incidence of congenital heart disease as well as the associated complications makes it necessary to establish a diagnosis as early as possible to adopt the most appropriate measures in a personalized approach. In this review, we provide an exhaustive update of the genetic bases of the most frequent congenital heart diseases as well as other syndromes associated with congenital heart defects, and how genetic data can be translated to clinical practice in a personalized approach.

show abstract

“…The most solid predictions can be made for CHD, with an 8%-13% diagnostic yield consistent among vast cohorts ranging from 197 to 610 samples [ 37 , 38 , 49 , 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Prenatal Exome Sequencing: Background, Current Practice and Future Perspectives—A Systematic Review

et al. 2021

View full text Add to dashboard Cite

The introduction of Next Generation Sequencing (NGS) technologies has exerted a significant impact on prenatal diagnosis. Prenatal Exome Sequencing (pES) is performed with increasing frequency in fetuses with structural anomalies and negative chromosomal analysis. The actual diagnostic value varies extensively, and the role of incidental/secondary or inconclusive findings and negative results has not been fully ascertained. We performed a systematic literature review to evaluate the diagnostic yield, as well as inconclusive and negative-result rates of pES. Papers were divided in two groups. The former includes fetuses presenting structural anomalies, regardless the involved organ; the latter focuses on specific class anomalies. Available findings on non-informative or negative results were gathered as well. In the first group, the weighted average diagnostic yield resulted 19%, and inconclusive finding rate 12%. In the second group, the percentages were extremely variable due to differences in sample sizes and inclusion criteria, which constitute major determinants of pES efficiency. Diagnostic pES availability and its application have a pivotal role in prenatal diagnosis, though more homogeneity in access criteria and a consensus on clinical management of controversial information management is envisageable to reach widespread use in the near future.

show abstract

COngenital heart disease and the Diagnostic yield with Exome sequencing (CODE) study: prospective cohort study and systematic review

Cited by 66 publications

References 45 publications

Prenatally detected isolated ventricular septum defects and the association with chromosomal aberrations—A nationwide register‐based study from Denmark

Prenatally detected isolated ventricular septum defects and the association with chromosomal aberrations—A nationwide register‐based study from Denmark

Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Prenatal Exome Sequencing: Background, Current Practice and Future Perspectives—A Systematic Review

Contact Info

Product

Resources

About