Atrioventricular Septal Defect in the Fetus – Associated Conditions and Outcome in 246 Cases

Berg, C. van den; Kaiser, Christy; Bender, F.; Geipel, A.; Kohl, Tobias; Axt-Fliedner, R; Krapp, M.; Knöpfle, G; Herberg, Ulrike; Breuer, Johannes; Schmitz, C; Gembruch, Ulrich

doi:10.1055/s-2008-1027438

Cited by 33 publications

(22 citation statements)

References 24 publications

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“…In one study, fetuses with DS and AVSD had a better survival rate than those with nonsyndromic AVSD, including a higher rate of successful surgical repair. 60 Although there are many possible developmental routes to AVSD, as indicated by mouse models, the findings in this study suggest that the VEGF-A pathway could play a predominant role in the cause of AVSD in DS. However, candidate-gene studies are by nature biased; thus, additional studies are required to determine the global role of the VEGF-A pathway in AVSD.…”

Section: Gata5mentioning

confidence: 62%

An Excess of Deleterious Variants in VEGF-A Pathway Genes in Down-Syndrome-Associated Atrioventricular Septal Defects

Ackerman

Locke

Feingold

et al. 2012

The American Journal of Human Genetics

102

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About half of people with trisomy 21 have a congenital heart defect (CHD), whereas the remainder have a structurally normal heart, demonstrating that trisomy 21 is a significant risk factor but is not causal for abnormal heart development. Atrioventricular septal defects (AVSD) are the most commonly occurring heart defects in Down syndrome (DS), and ∼65% of all AVSD is associated with DS. We used a candidate-gene approach among individuals with DS and complete AVSD (cases = 141) and DS with no CHD (controls = 141) to determine whether rare genetic variants in genes involved in atrioventricular valvuloseptal morphogenesis contribute to AVSD in this sensitized population. We found a significant excess (p < 0.0001) of variants predicted to be deleterious in cases compared to controls. At the most stringent level of filtering, we found potentially damaging variants in nearly 20% of cases but fewer than 3% of controls. The variants with the highest probability of being damaging in cases only were found in six genes: COL6A1, COL6A2, CRELD1, FBLN2, FRZB, and GATA5. Several of the case-specific variants were recurrent in unrelated individuals, occurring in 10% of cases studied. No variants with an equal probability of being damaging were found in controls, demonstrating a highly specific association with AVSD. Of note, all of these genes are in the VEGF-A pathway, even though the candidate genes analyzed in this study represented numerous biochemical and developmental pathways, suggesting that rare variants in the VEGF-A pathway might contribute to the genetic underpinnings of AVSD in humans.

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Section: Gata5mentioning

confidence: 62%

An Excess of Deleterious Variants in VEGF-A Pathway Genes in Down-Syndrome-Associated Atrioventricular Septal Defects

Ackerman

Locke

Feingold

et al. 2012

The American Journal of Human Genetics

102

View full text Add to dashboard Cite

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“…While in PSAIVS defect, the degree of RVH is determined by the size and type of the ventricular septal defect and is therefore predictable to some extent even in the intrauterine period [14][15][16][17][18][19][20][21][22][23], the likeliness of a univentricular (UV), or biventricular (BV) postnatal circulation in severe PSAIVS is much more difficult to predict. Postnatal series showed that RV size, TV size, and the coronary morphology are the most important determinants of UV or BV outcome [3,9,[24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Severe Pulmonary Stenosis or Atresia with Intact Ventricular Septum in the Fetus: The Natural History

et al. 2019

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Purpose: To assess the intrauterine course, the outcome, and to establish a new prenatal echocardiographic scoring system to predict biventricular (BV) versus univentricular (UV) outcome of fetuses with severe pulmonary stenosis or atresia with intact ventricular septum (PSAIVS). Methods: All cases of PSAIVS diagnosed prenatally over a period of 14 years were retrospectively collected in 2 tertiary referral centers. Results: Forty-nine fetuses with PSIVS (n = 11) or PAIVS (n = 38) were identified prenatally. Nineteen (38.8%) fetuses had additional ventriculocoronary connections (VCCs) and 21 (42.9%) fetuses had right ventricular hypoplasia. Four (8.2%) pregnancies were terminated, 2 (4.1%) ended in intrauterine fetal death, 4 (8.2%) in neonatal death, and 5 (10.2%) children died in infancy or childhood, including one case with compassionate care. Thirty-four of 44 (77.3%) fetuses with the intention-to-treat were alive at latest follow-up, 25 (73.5%) with BV, and 9 (26.5%) with UV circulation. Most significant predictive markers of UV circulation were Vmax of tricuspid regurgitation (TR) < 2 m/s, right ventricle/left ventricle length ratio ≤0.6, and presence of VCC. A scoring system including these 3 markers had 100% sensitivity and 100% specificity predicting an UV outcome if more than one of these criteria was fulfilled. All 25 liveborn infants that were suitable for BV repair survived, whereas only 9 out of 14 candidates for UV repair survived. None of the 14 fetuses with predicted UV outcome would have met the inclusion criteria for fetal intervention, as 10 of them had VCC and the remaining 4 had absent TR or Vmax < 2 m/s. Conclusion: The prognosis of prenatally diagnosed PSAIVS is good if BV circulation can be achieved, while postnatal mortality in UV circulation is high within the first 4 months of life. Postnatal outcome can be predicted prenatally with high accuracy using a simple scoring system. This information is mandatory for parental counseling and may be useful in selecting fetuses for intrauterine valvuloplasty.

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“…Normally, the early diagnosis of atrioventricular canal defect (AVCD) requires cardiological follow-up resulting in timely operative repair; the later the repair is made, the more loss of ventricular function occurs 3 – 5. In a retrospective review of all cases of atrioventricular septal defect (AVSD) detected prenatally between 1998 and 2006 in Germany, 246 cases of AVSD were detected in the study period: 129 (52.4%) cases had chromosomal anomalies, 72 (29.3%) heterotaxy syndromes 6. In 15% to 20% of cases patients with Klinefelter syndrome have a heart defect (usually patent ductus arteriosus) 7.…”

Section: Discussionmentioning

confidence: 99%

Atrioventricular Septal Defect in the Fetus – Associated Conditions and Outcome in 246 Cases

Cited by 33 publications

References 24 publications

An Excess of Deleterious Variants in VEGF-A Pathway Genes in Down-Syndrome-Associated Atrioventricular Septal Defects

An Excess of Deleterious Variants in VEGF-A Pathway Genes in Down-Syndrome-Associated Atrioventricular Septal Defects

Severe Pulmonary Stenosis or Atresia with Intact Ventricular Septum in the Fetus: The Natural History

Congenital defect of the partial atrioventricular canal with Klinefelter syndrome

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