Prenatal Diagnosis最新文献

Objective: Confined placental mosaicism (CPM) is associated with an increased risk for pregnancy complications, such as fetal growth restriction (FGR), preterm birth and hypertensive disorders. Pregnancies with possible CPM can be identified with non-invasive prenatal testing (NIPT). We performed a retrospective cohort study to investigate whether the mosaic ratio, as calculated with the Veriseq v2 used for NIPT, can predict adverse pregnancy outcomes in cases of CPM.

Method: A mosaic ratio for trisomies detected by NIPT and obstetric data such as fetal growth, structural fetal anomalies and birthweight were retrospectively studied in a cohort of patients with CPM diagnosed between February 2021 and October 2023. Structural and sex chromosomal aberrations were not included in this study.

Results: Of 122 CPM cases, 52 cases (42.6%) showed adverse perinatal outcomes, including FGR, low birthweight, hypertensive disorders, or preterm birth. A significantly higher mosaic ratio was found in the adverse outcome group compared to those with normal outcome, but a clear-cut threshold could not be set, except potentially for trisomy 16.

Conclusion: There is an association between the mosaic ratio and adverse pregnancy outcomes in cases of CPM. However, without a clear-cut threshold, it cannot be used for the individual patient for differentiation between CPM with and without clinical consequences.

Fetal two-dimensional speckle tracking echocardiography (2D-STE) is a novel technique that provides information on fetal heart function by measuring global longitudinal strain (GLS) and global longitudinal strain rate (GLSR). These features assess the longitudinal deformity of the fetal cardiac wall. 2D-STE is shown to be of prognostic value in children and adults with congenital heart disease (CHD). Therefore, its importance in fetal life should also be considered. This systematic review and meta-analysis provides an overview of the literature on 2D-STE (GLS/GLSR) in fetuses with CHD, focusing on the left and right ventricles (LV/RV). Findings indicated that LV-GLS was significantly lower in fetuses with coarctation of the aorta (CoA) and Tetralogy of Fallot (ToF) compared to controls. Conversely, fetuses with a single left ventricle exhibited higher LV-GLS. RV-GLS was significantly lower in fetuses with hypoplastic left heart syndrome (HLHS) and ToF compared to controls. LV-GLSR was significantly lower in fetuses with CoA. Overall, considerable heterogeneity was observed, possibly due to differences in study design. More prospective longitudinal studies on 2D-STE in fetuses with CHD, considering heterogeneity parameters, could offer better insights into this promising technique.

Objectives: To investigate the diagnostic utility of copy-number variant (CNV) detection by chromosomal microarray analysis (CMA) and genotype-phenotype associations in prenatal congenital anomalies of the kidney and urinary tract (CAKUT).

Methods: This is a retrospective multi-center study of CNV analysis in 457 fetuses with ultrasound-detected CAKUT and normal karyotypes. Cohorts from published studies were included for further pooled analyses (N = 2746). A literature review of single-nucleotide variant (SNV) and small insertions and deletions (Indel) analysis by whole-exome sequencing was performed to investigate monogenic causes.

Results: In our multi-center cohort, 5.3% (24/457) of fetuses had pathogenic CNVs (pCNV); 3.9% (14/359) and 10.2% (10/98) in isolated and non-isolated CAKUT, respectively. Fetuses with isolated hyperechogenic kidneys (HEK) had the highest incidence of having pCNVs. In the literature review, 6.6% (180/2746) of fetuses carried pCNVs; 6.1% and 7.5% in isolated and non-isolated CAKUT, respectively. SNV/Indel analysis provided at least 16.5% (63/381) additional diagnostic yield beyond CNV analysis; 12.8% and 23.8% in isolated and non-isolated CAKUT, respectively.

Conclusion: pCNVs comprise a significant proportion of genetic diagnostic findings in prenatal CAKUT, most commonly detected in fetuses with isolated HEK, MCDK, renal agenesis, and non-isolated CAKUT. Monogenic causes should be considered when karyotyping and CMA are nondiagnostic.

Rubinstein-Taybi syndrome (RSTS) is a rare syndrome characterized by intellectual disability, distinctive facial features and distal limb abnormalities. RSTS is indicated by clinical features and confirmed via genetic testing. In this prenatal case series, we report four cases of RSTS with various sonographic features. Some features, such as corpus callosum dysgenesis, are nonspecific, but they may be the first sign apparent, as they appear early in pregnancy. Others, like beaked nose, shawl scrotum, premature coccygeal ossification, and overly mature scrotal sac with excessive rugae, are distinctive, but they may only be apparent in advanced gestation.

Background: The aim of this study was to evaluate the diagnostic yield of routine exome sequencing (ES) in fetuses with ultrasound anomalies.

Methods: We performed a retrospective analysis of the ES results of 629 fetuses with isolated or multiple anomalies referred in 2019-2022. Variants in a gene panel consisting of approximately 3400 genes associated with multiple congenital anomalies and/or intellectual disability were analyzed. We used trio analysis and filtering for de novo variants, compound heterozygous variants, homozygous variants, X-linked variants, variants in imprinted genes, and known pathogenic variants.

Results: Pathogenic and likely pathogenic variants (class five and four, respectively) were identified in 14.0% (88/629, 95% CI 11.5%-16.9%) of cases. In the current cohort, the probability of detecting a monogenetic disorder was ∼1:7 (88/629, 95% CI 1:8.7-1:5.9), ranging from 1:9 (49/424) in cases with one major anomaly to 1:5 (32/147) in cases with multiple system anomalies.

Conclusions: Our results indicate that a notable number of fetuses (1:7) with ultrasound anomalies and a normal chromosomal microarray have a (likely) pathogenic variant that can be detected through prenatal ES. These results warrant implementation of exome sequencing in selected cases, including those with an isolated anomaly on prenatal ultrasound.

Objective: To assess the frequency of fetal therapy for fetuses with congenital pulmonary malformations (CPMs) and to investigate their short-term outcomes.

Method: The study population included 435 singleton fetuses diagnosed with CPMs from a national population-based cohort study in France in 2015-2018. Information was obtained from medical records on CPM volume ratio (CVR), signs of compression, fetal therapy and perinatal outcomes. The characteristics and outcomes of fetuses with and without fetal therapy were compared using a univariate test.

Results: Twenty six fetuses (6.0%, 95% CI: 4.1-8.6) received at least one fetal therapy including thoracoamniotic shunts only (n = 3), antenatal steroids only (n = 12), and a combination of several therapies including thoracentesis and amniodrainage, in addition to shunts and steroids (n = 11). Compared with fetuses without fetal therapy, those who did have higher CVR (1.6 ± 0.3 vs. 0.7 ± 0.04, p < 0.001) and more severe signs of compression (73.1% vs. 12.8%, p < 0.001). The proportion of live births after fetal therapy was 84.6% versus 98.5% (p < 0.001) for those without fetal therapy and the hospital mortality rate was 13.6% versus 1.0% (p = 0.004), respectively.

Conclusion: A small minority of fetuses with CPMs underwent fetal therapy. These patients had a lower survival compared with those who did not receive fetal therapy.

Trial registration: NCT02352207.

Objective: To quantify the uptake rates of Carrier Screening (CS) in consanguineous couples and compare this rate to that of non-consanguineous couples.

Methods: We performed a matched case control study of 82 consanguineous couples seen at Rutgers-Robert Wood Johnson Medical school who were offered carrier screening between January 1, 2012 and October 10, 2022. We then matched each consanguineous female patient to a non-consanguineous female control patient who was also offered CS at the time of their genetic counseling appointment. A 2 × 2 contingency table analysis was used to compare rates of acceptance and declination between the consanguineous and non-consanguineous groups.

Results: The overall acceptance rate among consanguineous couples was 82.9%, whereas the overall acceptance rate among non-consanguineous couples was 56.1%. After statistical analysis, consanguineous couples were significantly more likely to accept CS as compared to non-consanguineous couples (OR = 3.801, 95% CI; p < 0.0001). We also report the carrier couple rates and individual carrier statistics between these two groups.

Conclusion: This study supports the idea that consanguineous couples are more likely to pursue CS and have a higher carrier couple yield.

Background: Branchio-oto-renal (BOR) spectrum disorders are linked to pathogenic variants in the EYA1 gene, presenting significant challenges for prenatal ultrasound screening due to their phenotypic variability and complexity. Understanding these disorders' phenotypic expressions and genetic foundations is crucial.

Methods: Our study included pregnant women who underwent fetal whole-exome sequencing at the Department of Medical Genetics and Prenatal Diagnosis, The Third Affiliated Hospital of Zhengzhou University, Henan, China between January 2023 and March 2024. We identified a novel EYA1 gene pathogenic variant and conducted a systematic literature review of all reported prenatal cases associated with EYA1-related diseases, focusing on the detectability of these conditions in prenatal ultrasound. Additionally, we systematically reviewed case reports related to the EYA1 gene, emphasizing missense pathogenic variants for functional predictions and locus position analysis.

Results: Our research discovered a new pathogenic variant within the EYA1 gene, highlighting the difficulty of detecting BOR spectrum disorder phenotypes through prenatal ultrasound due to their subtle manifestations. We found that amniotic fluid anomalies and cardiac abnormalities are more prevalent in prenatal cases compared to postnatal cases. A critical region within the EYA Homologous Region (eyaHR) was identified, where missense pathogenic variants significantly affect protein stability, indicating a crucial area associated with the severity of phenotypic expression in EYA1 gene-associated disorders.

Conclusion: This study enhances the understanding of the genetic landscape of BOR spectrum disorders and suggests that certain phenotypic markers and genetic regions may be pivotal in improving prenatal screening and diagnosis for EYA1-related diseases.