Search

Objective: To analyze the risk for genetic aberrations and pregnancy outcomes in pregnancies with isolated polyhydramnios., Study Design: This was a retrospective study of singleton pregnancies complicated by isolated polyhydramnios that underwent genetic amniocentesis between 2016 and 2021. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, chromosomal microarray results, and pregnancy outcomes., Results: A total of 94 singleton pregnancies were included. Three (3.2%) cases with chromosomal abnormalities were detected, including 2 case of trisomy 21 and 1 of 22q21.1 microdeletion. One case was diagnosed as Prader-Willi syndrome caused by maternal uniparental disomy of chromosome 15. Perinatal death occurred in 1 case with severe polyhydramnios, and was retrospectively diagnosed as Bartter syndrome. Of the 90 infants survived, two were identified to have single gene disorders after birth by whole exome sequencing., Conclusion: We first attempted to determine the value of exome sequencing in pregnancies with isolated polyhydramnios. Our results warrant more studies to evaluate advanced genetic testing technologies used in such pregnancies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To present the prenatal features and postnatal outcomes of pregnancies with fetal nemaline myopathy (NM)., Study Design: This was a retrospective study of nine cases with NM diagnosed by prenatal or postnatal clinical features and confirmed by genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, exome sequencing (ES) results, and pregnancy outcomes., Results: All of the nine cases were detected to have NM-causing variants, involving NEB gene in 2 cases, ACTA1 in 3 cases, KLHL40 in 3 cases, and TPM2 in 1 case. Almost all (8/9) had normal first-trimester ultrasound scans except one who had an increased nuchal translucency. Seven (7/9) cases had second-trimester abnormal ultrasounds with fetal akinesia and/or extremity anomalies. Two (2/9) had only third-trimester abnormal ultrasounds with fetal akinesia and polyhydramnios, with one combined with fetal growth restriction. Four pregnancies with a positive prenatal ES were terminated, while five having not receiving prenatal ES continued to term. Only one infant survived 1 year old, and four passed away within 12 months., Conclusion: Prenatal ultrasound can detect clues that lead to the diagnosis of NM, such as reduced or absent fetal movements, polyhydramnios and extremity anomalies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To present the fetal features of Cornelia de Lange Syndrome (CdLS) with a molecular confirmation., Study Design: This was a retrospective study of 13 cases with CdLS diagnosed by prenatal and postnatal genetic testing and physical examination. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, chromosomal microarray and exome sequencing (ES) results, and pregnancy outcomes., Results: All of the 13 cases were detected to have a CdLS-causing variant, with 8 variants identified in the NIPBL gene, 3 in SMC1A, and 2 in HDAC8. Five had normal ultrasound scans during pregnancy; all were caused by variants of SMC1A or HDAC8. For the eight cases with NIPBL variants, all had prenatal ultrasound markers. Three had first trimester ultrasound markers including increased nuchal translucency in one and limb defects in three. Four presented with normal ultrasound in the first trimester, but abnormal ultrasound in the second trimester, including micrognathia in two, hypospadias in one and intrauterine growth retardation (IUGR) in one. IUGR as the isolated feature was identified in one case in the third trimester., Conclusion: The prenatal diagnosis of CdLS caused by NIPBLvariants is possible. It seems to remain challenging to detect non-classic CdLS only relying on ultrasound examination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To determine the fetal ultrasound findings associated with Sotos syndrome caused by deletions at 5q35 including the NSD1 and a point mutation in this gene., Study Design: This was a retrospective study of eight pregnancies with fetal Sotos syndrome identified by chromosomal microarray (CMA)/whole exome sequencing (WES). Clinical and laboratory data were collected and reviewed for these cases., Results: Two cases had no significant fetal abnormalities, and were only diagnosed after birth. One case presented in the first trimester with increased nuchal translucency. The remaining five fetuses were identified at late gestation. One of the five fetuses presented in the second trimester with mild ventriculomegaly, and four in the third trimester with mild ventriculomegaly, macrocephaly and polyhydramnios. CMA was done on all cases and revealed 5q35 deletions in seven cases, and WES detected a maternally inherited NSD1 variant in one case., Conclusion: The fetal ultrasound findings in cases with Sotos syndrome, associated with deletions at 5q35 and a point mutation in the NSD1 are not specific with the most common finding being mild ventriculomegaly., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To present the experience on prenatal diagnosis of Miller-Dieker syndrome (MDS)/PAFAH1B1-related lissencephaly to further determine fetal phenotypes of this syndrome., Study Design: This was a retrospective study of ten pregnancies with fetal MDS/PAFAH1B1-related lissencephaly identified by chromosomal microarray (CMA)/exome sequencing (ES). Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, CMA or ES results and pregnancy outcomes., Results: Two cases were diagnosed in the first trimester because of an increased nuchal translucency. The remaining eight cases were identified at late gestation, including four in the second trimester because of fetal cardiac anomalies or ventriculomegaly, and four in the third trimester because of ventriculomegaly. CMA revealed 17p13.3 deletions in nine cases, and ES detected a de novo PAFAH1B1 missense mutation in one case., Conclusion: The prenatal presentation of MDS/PAFAH1B1-related lissencephaly depended on the gestational age when the diagnosis was made. Mild ventriculomegaly was the most common prenatal sonographic sign identified in cases of MDS/PAFAH1B1-related lissencephaly. It is important that fetal MRI and invasive testing with CMA should be considered in fetuses with apparently 'isolated' mild ventriculomegaly., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To evaluate the prognosis of fetuses with a prenatal diagnosis of micrognathia in the first trimester., Study Design: Over a 3-year period, patients with fetal micrognathia were detected at the time of nuchal translucency screening. The medical records of these pregnancies were reviewed, including maternal demographics, sonographic findings, genetic testing results and pregnancy outcomes., Results: Forty-three cases of first-trimester micrognathia were included in this study. Chromosomal abnormalities were detected in seven cases. Of the fetuses with a normal array, further investigation of monogenic disorders with whole-exome sequencing was undertaken in 13 cases. Monogenic syndromes were identified in eight cases, including six with de-novo dominant alleles and two with recessive conditions. Whole-exome sequencing was refused in 23 cases; among these, other additional anomalies were found on anatomic ultrasound in 10 cases., Conclusion: This study demonstrated that caution should be adopted when finding an apparently isolated micrognathia in early gestation, even with a normal array. A diagnosis of genetic syndrome or multiple anomalies on subsequent scans is most likely, and will affect the final prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To determine monogenic syndromes in cases of fetal akinesia in order to understand the genetic aetiology., Study Design: Clinical trio exome sequencing (ES) was performed on DNA extracted from postnatal samples in 12 cases with fetal akinesia identified by prenatal ultrasound and a normal chromosomal micro-array analysis result. This test targets coding exons for 4200 clinically relevant disease-causing genes. The interpretation of variants was performed according to the guidelines of the American College of Medical Genetics., Results: A definite molecular diagnosis was achieved in six (50 %) of the 12 cases using clinical trio ES. In five cases, the pathogenic variants were located in known fetal-akinesia-associated genes. In one case, the underlying pathogenic variants were in known disease genes that had not been linked to fetal akinesia previously. Six pregnancies were terminated by the parents, and six pregnancies were continued to term., Conclusion: Genetic defects leading to fetal akinesia were found in half of the study cases using clinical trio ES. This information will be useful in genetic counselling with regard to prognosis and risk of recurrence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To report the experience on the clinical use of noninvasive cell-free (cf) DNA testing at late pregnancy., Study Design: A cohort of 1539 women with singleton gestations of ≥23 weeks receiving cfDNA testing in a 3-year period were included for this study. Maternal characteristics and data on cfDNA testing, confirming diagnostic testing and pregnancy outcome were reviewed., Results: During the study period, 1539 patients had cfDNA testing although they had a normal first-trimester screening. Of these, 7 cases had a positive result, including 5 for chromosome 21, one for chromosome 18, and one for chromosome 13. The most common indication was soft markers on ultrasound, followed by polyhydramnios. Cytogenetic testing was done for the 5 trisomy 21 positive cases, and confirmed the cfDNA results. Confirmative testing was declined in the two cases with positive cfDNA for trisomy 18/13, and postnatal placental investigation showed confined placental mosaicism with normal karyotype in the cord blood of newborns. There were no confirmed false negatives reported. The cfDNA screening achieved a positive predictive value of 71.4 % and a negative predictive value of 100 % in late pregnancy for common trisomies., Conclusions: There is no gestational age upper limit for cfDNA use in the clinical practice. Most of the time, cfDNA was used in late gestation for reassurance in patients who is at low risk for aneuploidies but had second-trimester soft markers on ultrasound., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The aim of this study is to review our institution's experience with fetal cardiac rhabdomyoma, and to document the prenatal genetic testing for tuberous sclerosis complex (TSC) and clinical outcome of the affected pregnancies., Study Design: During a four-year period, patients with fetal cardiac rhabdomyoma were detected by echocardiography in the second trimester of pregnancy. Molecular genetic analysis was conducted on fetuses to screen for variants of TSC1/TSC2 genes. We reviewed medical records of these affected pregnancies, including maternal demographics, sonographic findings, genotyping results and pregnancy outcomes., Results: Eleven cases with fetal cardiac rhabdomyoma were studied during the study period. A pathogenic variant of TSC1/TSC2 genes was detected in all cases, including two with an inherited variant and nine with a de novo variant. Out of these eleven cases diagnosed prenatally, eight pregnancies were terminated and three continued till term., Conclusions: Cardiac rhabdomyoma is the prenatal sign of TSC. A molecular investigation of TSC1/TSC2 genes should be recommended for fetuses with a rhabdomyoma and the parents, and the prognostic counselling should include TSC and its consequences., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To present the experience on prenatal diagnosis of Wolf-Hirschhorn syndrome (WHS) to further delineate the fetal presentation of this syndrome., Study Design: This was a retrospective analysis of ten pregnancies with fetal WHS identified by chromosomal microarray (CMA). Clinical data were reviewed for these cases, including maternal demographics, indications for invasive testing, sonographic findings, CMA results and pregnancy outcomes., Results: Three cases were diagnosed at the first trimester because of an increased NT or cystic hygroma. The remaining seven cases were identified at late gestation for abnormal ultrasound findings. CMA revealed 4p deletions to be terminal in all of the ten cases. Deletion sizes ranged from 2.05 to 19.02 Mb., Conclusion: Prenatal findings such as increased NT, severe and early onset intrauterine growth retardation, and renal dysplasia or oligohydramnios should warrant the diagnosis of WHS and invasive testing using CMA., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To evaluate the potential of maternal serum placental growth factor (PlGF) as a marker for Trisomy 21 in Chinese pregnant women., Study Design: Serum samples were collected and stored from 600 women who have a viable singleton pregnancy and underwent first trimester screening for Trisomy 21 between 2011 and 2014. Serum concentration of PlGF was measured using the automated time-solved immunofluorometric assay and expressed as Multiples of the expected median (MoM) from the 600 women available stored serum samples (558 Euploidy and 42 Trisomy 21). The levels of PlGF MoM were compared between Trisomy 21 cases and Euploid pregnancies. Expected median PlGF levels in Chinese were also compared to that published for Caucasians. Multivariate Gaussian modeling was performed to predict detection and false-positive rates., Results: In euploid pregnancies the concentrations of PlGF increased with Crown Rump Length(CRL) and decreased with maternal weight. The overall median MoM of PlGF in Chinese was higher than that of Caucasian. The median PlGF level was 0.63 MoM in the cases and 1.00 MoM in the controls (p<0.0001). The prediction of Trisomy 21 has been slightly improved by the addition of PlGF to the standard screening test in China. The detection rate of screening after adding PlGF data was increased from 93.4% to 94.6% at a false-positive rate of 3% and the false positive rate decreased from 0.23% to 0.17% for a detection rate of 80%., Conclusion: The median PlGF concentrations in Chinese is higher than those of Caucasians. Results suggest adding PlGF may substantially improve the performance of current first trimester screening strategy for Trisomy 21 in Chinese pregnant women., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess the clinical value of prenatal diagnosis of fetuses with increased nuchal translucency (NT) using an approach based on quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray (CMA)., Study Design: From January 2013 to October 2014, we included 175 pregnancies with fetal NT ≥ 3.5mm at 11-13 weeks' gestation who received chorionic villus sampling. QF-PCR was first used to rapidly detect common aneuploidies. The cases with a normal QF-PCR result were analyzed by CMA., Results: Of the 175 cases, common aneuploidies were detected by QF-PCR in 53 (30.2%) cases (30 cases of trisomy 21, 12 cases of monosomy X, 7 cases of trisomy 18, 3 cases of trisomy 13 and 1 case of 47, XXY). Among the 122 cases with a normal QF-PCR result, microarray detected additional pathogenic copy number variants (CNVs) in 5.7% (7/122) of cases. Four cases would have expected to be detectable by conventional karyotyping because of large deletions/duplications (>10 Mb), leaving three cases (2.5%; 3/118) with pathogenic CNVs only detectable by CMA., Conclusion: It is rational to use a diagnostic strategy in which CMA is preceded by the less expensive, rapid, QF-PCR to detect common aneuploidies. CMA allows detection of a number of pathogenic chromosomal aberrations in fetuses with a high NT., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine the influence of free invasive prenatal testing on the uptake of non-invasive prenatal testing (NIPT)., Study Design: Over a 2-year period at a Chinese tertiary prenatal diagnostic unit, women at risk of fetal trisomy were given the option of NIPT or invasive prenatal testing. Invasive prenatal testing was offered free of charge to women with a local Hukou (household registration); however, women without a local Hukou were charged for invasive prenatal testing. Both women with and without a local Hukou were charged for NIPT., Results: During the first year, 2647 women with a positive trisomy 21 screening test were referred (474 women with a local Hukou and 2173 women without a local Hukou). Only 1.6% of the women with a local Hukou underwent NIPT, while this proportion was 20.6% in the women without a local Hukou. During the second year, the price of NIPT was reduced. The total number of women referred was 3047 (502 women with a local Hukou and 2545 women without a local Hukou). The uptake of NIPT in women without a local Hukou doubled, but the uptake of NIPT remained stable in women with a local Hukou., Conclusion: The financial impact on the uptake of NIPT should not be underestimated., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the efficacy of the sonographic cardiothoracic ratio (CTR) in early pregnancy for the prediction of fetal haemoglobin (Hb) Bart's disease., Study Design: Over a 1.5-year period at a Chinese tertiary obstetric centre, women at risk of Hb Bart's disease were given the option of a non-invasive approach to exclude an affected pregnancy between 11 weeks and 13 weeks and 6 days of gestation, with a routine rescan after a 2-week interval. The fetal CTR, a sonographic marker, was assessed, and invasive testing followed in cases of fetal cardiomegaly. The diagnosis of fetal Hb Bart's disease was based on DNA analysis from chorionic villus sampling., Results: Of 154 at-risk cases studied, five cases (four at 11 weeks of gestation) were subjected to direct invasive testing because of an unsatisfactory scan. Of the remaining 149 cases, non-invasive ultrasound examinations were performed successfully. Thirty-four (22.8%) affected pregnancies were revealed, including one picked up on rescan. The sensitivity and specificity of the non-invasive approach were 97.1% and 100%, respectively. The need for an invasive test was reduced by 74.7%, and all affected pregnancies except one were diagnosed before 14 weeks of gestation., Conclusion: CTR can differentiate reliably between pregnancies with and without Hb Bart's disease. This non-invasive approach for the exclusion of Hb Bart's disease can be used in early pregnancy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To apply a simple and low-cost approach, which would easily and accurately detect both the common chromosomal abnormalities and maternal cell contamination (MCC) when invasive prenatal testing is performed for diagnosis of thalassemia., Study Design: Quantitative fluorescence-polymerase chain reaction (QF-PCR) was carried out by amplification of microsatellite markers using fluorescence-labelled primers, followed by quantitative analysis of the allele peaks on a genetic analyser. A multiplex of 11 primer pairs for loci on each of chromosomes 13, 18 and 21 was used., Results: A total of 387 prenatal samples were tested. Five (1.3%) samples showed MCC, including two (0.7%, 2/289) amniotic fluid samples and three (3.1%; 3/98) chorionic villi samples. Of the 379 prenatal samples without MCC, QF-PCR assays detected two (0.5%) cases of trisomy 21, which were confirmed by traditional karyotyping, and missed one case of trisomy 2 mosaicism and one case of monosomy X. The case of trisomy 2 mosaicism was later found to be limited to the placenta, and the case of monosomy X was picked up by ultrasound. There was no clinically significant case that would have been missed if QF-PCR had been used as a stand-alone test instead of karyotyping when invasive prenatal testing was performed for diagnosis of thalassaemia., Conclusions: The QF-PCR assay could allow simultaneous detection of aneuploidy and possible MCC in the fetal material. This is especially valuable when PCR-based techniques are used in the DNA analysis for thalassaemia. This strategy may be applied to prenatal diagnosis of other recessive disorders.