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The prevalence of genetic diagnoses in fetuses with severe congenital heart defects. / van Nisselrooij, Amber E. L.; Lugthart, Malou A.; Clur, Sally-Ann et al.

In: Genetics in medicine, Vol. 22, No. 7, 01.07.2020, p. 1206-1214.

Research output: Contribution to journal › Article › Academic › peer-review

Harvard

van Nisselrooij, AEL, Lugthart, MA, Clur, S-A, Linskens, IH, Pajkrt, E, Rammeloo, LA, Rozendaal, L, Blom, NA, van Lith, JMM, Knegt, AC, Hoffer, MJV, Aten, E, Santen, GWE & Haak, MC 2020, 'The prevalence of genetic diagnoses in fetuses with severe congenital heart defects', Genetics in medicine, vol. 22, no. 7, pp. 1206-1214. https://doi.org/10.1038/s41436-020-0791-8

APA

van Nisselrooij, A. E. L., Lugthart, M. A., Clur, S-A., Linskens, I. H., Pajkrt, E., Rammeloo, L. A., Rozendaal, L., Blom, N. A., van Lith, J. M. M., Knegt, A. C., Hoffer, M. J. V., Aten, E., Santen, G. W. E., & Haak, M. C. (2020). The prevalence of genetic diagnoses in fetuses with severe congenital heart defects. Genetics in medicine, 22(7), 1206-1214. https://doi.org/10.1038/s41436-020-0791-8

Vancouver

van Nisselrooij AEL, Lugthart MA, Clur S-A, Linskens IH, Pajkrt E, Rammeloo LA et al. The prevalence of genetic diagnoses in fetuses with severe congenital heart defects. Genetics in medicine. 2020 Jul 1;22(7):1206-1214. Epub 2020. doi: 10.1038/s41436-020-0791-8

Author

van Nisselrooij, Amber E. L. ; Lugthart, Malou A. ; Clur, Sally-Ann et al. / The prevalence of genetic diagnoses in fetuses with severe congenital heart defects. In: Genetics in medicine. 2020 ; Vol. 22, No. 7. pp. 1206-1214.

BibTeX

@article{5905f739690443c89d3933d118a25966,
title = "The prevalence of genetic diagnoses in fetuses with severe congenital heart defects",
abstract = "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.",
keywords = "chromosome microarray analysis, congenital heart defects, exome sequencing, genetic syndrome, prenatal counseling",
author = "{van Nisselrooij}, {Amber E. L.} and Lugthart, {Malou A.} and Sally-Ann Clur and Linskens, {Ingeborg H.} and Eva Pajkrt and Rammeloo, {Lukas A.} and Lieke Rozendaal and Blom, {Nico A.} and {van Lith}, {Jan M. M.} and Knegt, {Alida C.} and Hoffer, {Mari{\"e}tte J. V.} and Emmelien Aten and Santen, {Gijs W. E.} and Haak, {Monique C.}",
year = "2020",
month = jul,
day = "1",
doi = "10.1038/s41436-020-0791-8",
language = "English",
volume = "22",
pages = "1206--1214",
journal = "Genetics in medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

RIS

TY - JOUR

T1 - The prevalence of genetic diagnoses in fetuses with severe congenital heart defects

AU - van Nisselrooij, Amber E. L.

AU - Lugthart, Malou A.

AU - Clur, Sally-Ann

AU - Linskens, Ingeborg H.

AU - Pajkrt, Eva

AU - Rammeloo, Lukas A.

AU - Rozendaal, Lieke

AU - Blom, Nico A.

AU - van Lith, Jan M. M.

AU - Knegt, Alida C.

AU - Hoffer, Mariëtte J. V.

AU - Aten, Emmelien

AU - Santen, Gijs W. E.

AU - Haak, Monique C.

PY - 2020/7/1

Y1 - 2020/7/1

N2 - 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.

AB - 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.

KW - chromosome microarray analysis

KW - congenital heart defects

KW - exome sequencing

KW - genetic syndrome

KW - prenatal counseling

UR - http://www.scopus.com/inward/record.url?scp=85084133900&partnerID=8YFLogxK

U2 - 10.1038/s41436-020-0791-8

DO - 10.1038/s41436-020-0791-8

M3 - Article

C2 - 32341573

VL - 22

SP - 1206

EP - 1214

JO - Genetics in medicine

JF - Genetics in medicine

SN - 1098-3600

IS - 7

ER -

ID: 11531539