Accurate Prenatal Diagnosis Research Articles

Incremental yield of prenatal exome sequencing in fetuses with skeletal system abnormalities: A systematic review and meta-analysis.

Fetal skeletal abnormalities can be caused by various factors and genetic cause plays an important role. Prenatal exome sequencing (ES) has been shown to be a powerful approach for accurate prenatal molecular diagnoses. Diagnostic yield of ES in fetal skeletal abnormalities varies significantly across studies. This study aimed to perform a systematic review of the literature and meta-analysis to assess the incremental yield of ES in fetuses with different kinds of skeletal abnormalities and a negative result on chromosome microarray or karyotyping. The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched up to November 26, 2022. Relevant data were collected from observational studies containing five or more cases of skeletal abnormalities who underwent ES. The incremental yield of ES was evaluated by single proportion analysis and 95% confidence interval (CI), both according to the article features and individual phenotypes. This study was registered on PROSPERO as CRD42022382800. Twenty-six studies including 524 individuals met the inclusion criteria. The pooled incremental yield was 60.2% (95% CI, 53.4%-66.9%) for all fetuses with skeletal abnormalities. In subgroup analysis, the additional diagnostic yield was 83.9% (95% CI, 76.4%-90.4%) in isolated dysplasia cases (group I), 52.0% (95% CI, 32.9%-70.9%) in dysplasia with non-skeletal abnormalities cases (group II), 33.3% (95% CI, 19.3%-48.6%) in isolate dysostoses cases (group III), 47.8% (95 % CI, 35.8%-60.0%) in dysostoses with non-skeletal abnormalities cases (group IV), 83.0% (95% CI, 63.7%-97.1%) in combination of the two phenotypes without non-skeletal abnormalities cases (group V), 74.5% (95% CI, 54.9%-90.9%) in combination of the two phenotypes with non-skeletal abnormalities cases (group VI). The origin of the pathogenic variations differed among the groups. Most causative variants were de novo in groups I (97/133, 72.9%), V (14/23, 60.9%), and VI (15/26, 57.7%). Meanwhile, pathogenic variations in III (18/25, 72.0%) and IV (37/67, 55.2%) were more often inherited from a parent. ES had a favorable incremental yield in fetuses with skeletal abnormalities. The common pathogenic variations and genetic patterns of skeletal abnormalities vary among different subtypes. Interpreting this difference is beneficial for personalized clinical consultation.

Prenatal diagnosis of fetal skeletal anomalies via whole-exome sequencing in a tertiary referral center

The accurate prenatal diagnosis of skeletal anomaly (SKA) using prenatal imaging alone remains challenging. We aimed to investigate the efficacy of whole-exome sequencing (WES) in the prenatal molecular genetic diagnosis of skeletal system abnormalities, with or without additional ultrasound anomalies. All fetuses with SKA were subjected to sequential genetic tests, and after excluding fetal chromosomal abnormalities and clinically significant copy number variations (CNVs) consistent with the observed phenotype, the affected fetuses were further subjected to WES. The clinical features of fetal SKA were collected, and the results of molecular genetic testing and perinatal outcomes were analyzed. Following negative routine genetic test results of the 78 fetuses, trio-WES was conducted for 73 fetuses, and fetus-only WES (single WES) was performed for five fetuses due to parental refusal. Fetal skeletal system abnormalities in our cohort were subdivided into seven groups: 39 (50%) had short long bones, 14 (17.9%) had abnormal limb morphology, 4 (5.1%) had polydactyly, 4 (5.1%) had the absence of the radius tibia or tibiofibula, 5 (6.4%) had spine anomalies, 6 (7.7%) had strephenopodia, and 6 (7.7%) had multiple deformities. In total, we identified the molecular diagnoses for 32/78 fetuses with SKAs, and confirmed 41 pathogenic/likely pathogenic variants in 28 genes, including nine novel variants in our cohort. The overall diagnostic rate was 41% (32/78). Our findings demonstrate that WES can greatly improve the genetic diagnostic rate of fetal SKAs following routine genetic testing, which can comprehensively guide perinatal management and help assess the risk of recurrence in future pregnancies. Our data also provide a basis for the association between the SKA phenotype and related genotypes and expand the spectrum of fetal SKA phenotypes and related genes.

Application of Genetic Origin Analysis of Copy Number Variations in Non-Invasive Prenatal Testing.

This study aimed to assess the application of origin analysis of copy number variations (CNVs) in non-invasive prenatal testing (NIPT) and provide a basis for expanding the clinical application of NIPT. We enrolled 35,317 patients who underwent NIPT between January 2019 and March 2023. Genome sequencing of copy number variation (CNV-Seq) analysis was performed using the CNV calling pipeline to identify subchromosomal abnormalities in maternal plasma. Genetic origin was determined by comparing the chimaerism ratio of CNV and the concentration of cell-free foetal DNA (cffDNA). All pregnant women with a high risk of CNV, as indicated by the NIPT, were informed of their genetic origins. Amniocentesis was recommended for detecting the CNVs in foetal chromosomes, and pregnancy outcomes were tracked. A total of 109 pregnancies showed clinically significant positive results for CNV after NIPT, including 65 cases of maternal/foetal (M/F)-CNVs and 44 cases of F-CNVs. The occurrence of M/F-CNVs was independent of age, screening (serological or ultrasound) indications for abnormalities, and mode of pregnancy. The incidence of pathogenic/likely pathogenic (P/LP)-F-CNVs was high in cases where serological screening indicated intermediate, high-risk, or abnormal US findings (p<0.05). In the M/F-CNV group, most of the P/LP-CNVs were small fragments with low penetrance; 55 (84.62%) were less than 5Mb in size, and nine (13.85%) were between 5 and 10Mb. In the F-CNV group, foetal P/LP-CNV was detected in 36 of 42 cases undergoing prenatal diagnosis, and no significant bias was noted in the size distribution of P/LP-F-CNV fragments. The prenatal diagnostic rate and positive predictive value in the F-CNV group were 95.45% and 85.71%, respectively, which were significantly different from those in the M/F group (26.15% and 52.95%), respectively (p<0.05). Genetic origin analysis of CNV can effectively improve adherence to prenatal diagnosis in pregnant women and the accuracy of prenatal diagnosis.

Current approaches to prenatal imaging of lung malformations: a review

INTRODUCTION: Congenital lung malformations are result of developmental disorders at any stage of organ formation. Manifestations of these changes vary significantly: from minimal in size to large space-occupying lesion of the lung, which can cause fetal death or severe postnatal respiratory disorders. In proper time and accurate prenatal diagnosis of lung development abnormalities is one of the fundamental factors determining management of pregnancy and prognosis.OBJECTIVE: To demonstrate the most typical features of a wide range of congenital lung anomalies by ultrasound and MRI.MATERIALS AND METHODS: The literature search was performed in open Russian and English databases Medline, PubMed, Web of Science, RSCI, eLIBRARY using keywords and phrases: «prenatal diagnosis», «fetal MRI», «ultrasound diagnostics», «сongenital lung malformations».RESULTS: Based on literature data and our own experience in the use of ultrasound and MRI in diagnosis of сongenital lung malformations, the main signs of normal development and the most specific types of lung anomalies are described. Algorithm for diagnostic search for congenital lung malformations is presented.CONCLUSION: Ultrasound is the main method for diagnosing congenital lung anomalies. Fetal MRI is used to clarify the nature and extent of changes, a more detailed assessment of adjacent organs, also to determine Multiple congenital anomalies. Understanding the characteristics of semiotics of lung malformations and the main signs of these anomalies is a fundamental criterion for prenatal counseling, as well as peri- and postnatal management of this category of patients.

The onset of coarctation of the aorta before birth: Mechanistic insights from fetal arch anatomy and haemodynamics

Accurate prenatal diagnosis of coarctation of the aorta (CoA) is challenging due to high false positive rate burden and poorly understood aetiology. Despite associations with abnormal blood flow dynamics, fetal arch anatomy changes and alterations in tissue properties, its underlying mechanisms remain a longstanding subject of debate hindering diagnosis in utero. This study leverages computational fluid dynamics (CFD) simulations and statistical shape modelling to investigate the interplay between fetal arch anatomy and blood flow alterations in CoA. Using cardiac magnetic resonance imaging data from 188 fetuses, including normal controls and suspected CoA cases, a statistical shape model of the fetal arch anatomy was built. From this analysis, digital twin models of false and true positive CoA cases were generated. These models were then used to perform CFD simulations of the three-dimensional fetal arch haemodynamics, considering physiological variations in arch shape and blood flow conditions across the disease spectrum. This analysis revealed that independent changes in the shape of.the arch and the balance of left-to-right ventricular output led to qualitatively similar haemodynamic alterations. Transitioning from a false to a true positive phenotype increased retrograde flow through the aortic isthmus. This resulted in the appearance of an area of low wall shear stress surrounded by high wall shear stress values at the flow split apex on the aortic posterior wall opposite the ductal insertion point.Our results suggest a distinctive haemodynamic signature in CoA characterised by the appearance of retrograde flow through the aortic isthmus and altered wall shear stress at its posterior side. The consistent link between alterations in shape and blood flow in CoA suggests the need for comprehensive anatomical and functional diagnostic approaches in CoA. This study presents an application of the digital twin approach to support the understanding of CoA mechanisms in utero and its potential for improved diagnosis before birth.

Prenatal diagnosis of recurrent Kagami–Ogata syndrome inherited from a mother affected by Temple syndrome: a case report and literature review

BackgroundKagami–Ogata syndrome (KOS) and Temple syndrome (TS) are two imprinting disorders characterized by the absence or reduced expression of maternal or paternal genes in the chromosome 14q32 region, respectively. We present a rare prenatally diagnosed case of recurrent KOS inherited from a mother affected by TS.Case presentationThe woman’s two affected pregnancies exhibited recurrent manifestations of prenatal overgrowth, polyhydramnios, and omphalocele, as well as a small bell-shaped thorax with coat-hanger ribs postnatally. Prenatal genetic testing using a single-nucleotide polymorphism array detected a 268.2-kb deletion in the chromosome 14q32 imprinted region inherited from the mother, leading to the diagnosis of KOS. Additionally, the woman carried a de novo deletion in the paternal chromosome 14q32 imprinted region and presented with short stature and small hands and feet, indicating a diagnosis of TS.ConclusionsGiven the rarity of KOS as an imprinting disorder, accurate prenatal diagnosis of this rare imprinting disorder depends on two factors: (1) increasing clinician recognition of the clinical phenotype and related genetic mechanism, and (2) emphasizing the importance of imprinted regions in the CMA workflow for laboratory analysis.

Accurate prenatal diagnosis of coarctation of the aorta by 3-step echocardiographic diagnostic protocol

BackgroundCoarctation of the aorta (CoA) is the most common undiagnosed congenital heart defect during prenatal screening. High false positive and false negative rates seriously affect prenatal consultation and postnatal management. The objective of the study was to assess the utility of various measurements to predict prenatal CoA and to derive a diagnostic algorithm.MethodsOne hundred and fifty-four fetuses with suspected CoA who presented at Fuwai Hospital between December 2017 and August 2021 were enrolled and divided into confirmed CoA cases (n = 47) and false positive cases (n = 107), according to their postnatal outcomes. The transverse aortic arch, isthmus, and descending aorta were measured in the long-axis view of the aortic arch. The angle between the transverse aortic arch (TAO) and the descending aortic arch (DAO) was defined as the TAO-DAO angle and measured in the long axis or sagittal view. Based on the database in GE Voluson E10 and the formula (Z = \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{\ ext{x}-{\\mu }}{\\alpha }$$\\end{document}), the standard score (Z-score) of the dimensions of the aorta were calculated in relation to the gestational age. The main echocardiographic indices were combined to design a 3-step diagnostic protocol. The TAO-DAO angle was used as the first step in the diagnostic model. The diameter of the transverse arch and the Z-score of the isthmus were the second step. The third-step indices included a Z-score of the transverse arch, diameter of the isthmus, distance from the left subclavian artery (LSA) to left common carotid artery (LCCA), the ratio of isthmus diameter and LSA diameter and ratio of the distances (the distance between the LSA and LCCA to the distance between the right innominate artery and LCCA). The receiver operating characteristic (ROC) curve determined the predictive capability of each diagnostic parameter, and the kappa test determined the diagnostic accuracy of the proposed model.ResultsThe cases with confirmed CoA had thinner transverse arches (1.92 ± 0.32 mm vs. 3.06 ± 0.67 mm, P = 0.0001), lower Z-scores of the isthmus (-8.97 ± 1.45 vs. -5.65 ± 1.60, P = 0.0001), smaller TAO-DAO angles (105.54 ± 11.51° vs. 125.29 ± 8.97°, P = 0.0001) and larger distance between the LSA and LCCA (4.45 ± 1.75 mm vs. 2.74 ± 1.07 mm, P = 0.0001) than the false positive cases. The area under the curve (AUC) was 0.947 (95% CI 0.91–0.98) for the TAO-DAO angle ≤ 115.75°, 0.942 (95% CI 0.91–0.98) for the transverse arch diameter ≤ 2.31 mm, 0.937 (95% CI 0.90–0.98) for the Z-score of the isthmus ≤ -7.5, and 0.975 (95% CI 0.95–1.00) for the 3-step diagnostic protocol with 97.8% sensitivity and 97.2% specificity. The kappa test showed that the model’s diagnostic accuracy was consistent with postnatal outcomes (kappa value 0.936, P = 0.0001).ConclusionsThe 3-step diagnostic protocol included the three most useful measurements and the additional indices with appropriate cut-off values. The algorithm is useful for the detection of aortic coarctation in fetuses with a high degree of accuracy.Trial registrationRetrospectively registered.

Investigation of Spinocerebellar Ataxia (SCA) Disease in Iranian Patients and Accurate Trinucleotide Repeat Detection in the SCA3 by TP-PCR Method.

SCA (spinocerebellar ataxia) which is autosomal dominantly transferred is a subset of inherited cerebellar ataxia. These progressive neurological diseases have clinical features of ataxia and are derived from the destruction of the cerebellum. These diseases can also affect other areas, including the brainstem. Frequent proliferation of CAG nucleotides can encode polyglutamine and, as a result, produce the toxic polyglutamine (poly Q) protein that leads to many types of SCAs. They are categorized based on specific genetic mutations. The main symptoms of SCA, gait ataxia and incoordination, nystagmus, vision problems, and dysarthria, can be mentioned. In this study, 31 Iranians who were suspected of SCA disease were clinically diagnosed from November 2019 to September 2021. For these 31 patients suspected of spinocerebellar ataxia, PCR was performed, and the analysis was based on vertical electrophoresis. For SCA3 patients, the TP-PCR technique was carried out and evaluated by capillary electrophoresis. For all 31 patients, PCR function was successful according to the results attained by conventional PCR. The number of three nucleotide replications was within the normal range for 22 people, and nine patients were reported. Studies showed that three people suspected of SCA were infected with SCA3 according to the TP-PCR technique, and this was while seven people were diagnosed with SCA3 using the PCR method. As the purpose of this test is to provide a more accurate diagnostic method and prenatal diagnosis of this disease, the TP-PCR method proved to be more suitable when applied for the diagnosis of abnormal trinucleotides CAG in spinocerebellar ataxia type 3.

Prenatal Diagnosis of Poretti-Boltshauser Syndrome - a Case Report of a Molar Tooth Sign Mimic.

We report the prenatal diagnosis of Poretti-Boltshauser Syndrome (PBS) in a 36-year-old primigravida woman. At 22 weeks and 6 days of gestation, fetal ultrasound revealed a normally shaped but hyperechogenic cerebellum with all supratentorial structures appearing normal. Differential diagnosis included cavernous hemangioma, capillary telangiectasia, and cerebellar hemorrhage. Subsequent fetal cerebral MRI showed diffuse bilateral cerebellar modifications, reduced cranio-caudal diameter of the vermis, and pathological elongation and thickening of the superior cerebellar peduncles indicative of the molar tooth sign. Amniocentesis and whole exome sequencing identified two heterozygous truncating variants in the LAMA1 gene: c.3099G > A (p.Trp1033Ter) and c.3699T > A (p.Tyr1233Ter), confirming PBS.) Following the diagnosis, the pregnancy was terminated at 23 weeks and 5 days. Post-mortem examination supported the MRI findings consistent with PBS. This case highlights the importance of integrating ultrasound, MRI, and genetic analysis for accurate prenatal diagnosis and emphasizes the molecular diversity associated with PBS, including the presence of molar tooth sign mimics and a novel c.3699T > A variant.

Fast, portable and sensitive detection of group B streptococcus DNA using one-pot MIRA-CRISPR system with suboptimal PAM

The group B Streptococcus (GBS) can generate vertical transmission to infants during delivery, has been seriously threatening the health of infants. Rapid and accurate prenatal GBS diagnosis for pregnant women is a deterministic blueprint to avoid infant viruses. Here, we developed an extraction-free nucleic acid isothermal amplification/CRISPR-Cas12a cutting one-pot system for GBS diagnostic assay by using suboptimal protospacer adjacent motifs, effectively avoiding multiple handling steps and uncapping contamination. The GBS diagnosis assay based on a one-pot system was validated by using fluorescent technique and lateral flow assay strips, exhibited fantastic specificity, accuracy and sensitivity with a limit of detection of 32 copies per reaction (0.64 copies/μL). Moreover, a portable device was constructed and integrated with the one-pot system to realize the GBS detection without professional and scene restrictions, it showed excellent performance in clinical sample detection, which achieved optical and portable GBS detection for point-of-care testing or home-self testing.

Analysis of PAH gene variants and prenatal diagnosis for 43 Chinese pedigrees affected with Phenylketonuria

To explore the characteristics of phenylalanine hydroxylase (PAH) gene variants and prenatal diagnosis for 43 Chinese pedigrees affected with Phenylketonuria (PKU). Forty three PKU pedigrees diagnosed at the First Affiliated Hospital of Zhengzhou University between 2019 and 2021 were selected as the study subjects. Variants of the PAH gene of the probands were screened by high-throughput sequencing, and candidate variants were verified by Sanger sequencing. Negative cases were further analyzed by multiplex ligation-dependent probe amplification (MLPA) to detect large fragment deletions and duplications of the PAH gene. For 43 women undergoing subsequent pregnancy, Sanger sequencing, MLPA, combined with short tandem repeats (STR) sequence-based linkage analysis, were carried out for prenatal diagnosis. Among the 86 alleles carried by the 43 probands, 78 nucleotide variants (90.70%) and 3 large deletions (3.49%) were found based on high-throughput sequencing and MLPA. The 81 mutant alleles had included 21 missense variants, 5 splice site variants, 4 nonsense variants, 2 microdeletions, 1 insertional variant and 2 large fragment deletions. Relatively common variants have included p.Arg243Gln (23.26%), p.Arg111Ter (8.14%), EX6-96A>G (6.98%), p.Val399Val (5.81%) and p.Arg413Pro (4.65%). Most of the variants were located in exons 7, 11, 3, 6 and 12. For the 43 families undergoing prenatal diagnosis, 9 fetuses (20.45%) were diagnosed with PKU, 20 (45.45%) were heterozygous carriers, and 15 (34.09%) did not carry the same pathogenic allele as the proband. All neonates were followed up till 6 months old, and the accuracy of prenatal diagnosis was 100%. The combination of high-throughput sequencing, Sanger sequencing, MLPA and linkage analysis can increase the diagnostic rate of PKU and attain accurate prenatal diagnosis.

Diagnostic Methods for the Prenatal Detection of Cleft Lip and Palate: A Systematic Review.

Background: Accurate prenatal diagnosis of cleft lip and palate is essential to discuss severity prediction, perform appropriate parental counseling, and, at last, establish long-term treatment planning. The aim of this systematic review was to analyze the accuracy of various imaging techniques for the prenatal diagnosis of cleft lip and palate, assess the pregnancy phase for orofacial clefts diagnosis, and study the different cleft types in terms of diagnostic methods, timing, and predictability. Methods: A search of the PubMed, EMBASE, Scopus, and Web of Science databases was conducted to identify potentially relevant studies published until January 2024. The quality of the selected articles was assessed using the Newcastle-Ottawa scale for methodological quality assessment of cohort studies and the QUADAS-2 scale for diagnostic test studies. Results: A total of 18 studies met the eligibility criteria and were included in the review. The findings of this review indicate that the majority of studies showed improved diagnostic accuracy when supplementary techniques, such as 3D ultrasound or magnetic resonance imaging, were added to 2D ultrasound. Conclusions: The implementation of magnetic resonance imaging as a standard procedure could significantly improve the precision of diagnosing cleft lip and palate. Therefore, the diagnostic technique used will play a crucial role in the accuracy of the diagnosis.

Prenatally Diagnosed Congenital High Airway Obstruction Syndrome: Perinatal Management and Outcome—A Single Tertiary Care Center Experience

AbstractTo report our experience with the management of prenatally diagnosed cases of congenital high airway obstruction syndrome (CHAOS) and the postnatal outcome of those who underwent an ex utero intrapartum treatment (EXIT) procedure. This is a single center, retrospective observational study of prenatally diagnosed CHAOS cases using two-dimensional ultrasound from December 2017 to December 2022 in a tertiary care facility. Of the total nine fetuses prenatally diagnosed with CHAOS, three (33.3%) were associated with multiple congenital anomalies, seven out of nine (77.8%) developed ascites, and one had fetal hydrops. Five (55.6%) underwent medical termination of pregnancy and two were lost to follow-up (22.2%). The remaining two continued pregnancy and required EXIT tracheostomy at the time of delivery (22.2%). Microarray was performed in both which was normal. Postnatally, both infants are tracheostomy dependent with one requiring frequent ventilator support. CHAOS even when isolated generally has poor prognosis without intervention. Performing an EXIT procedure at birth can significantly improve postnatal survival by minimizing hypoxic damage. However, the long-term medical and surgical challenges for survivors remain numerous especially speech disorders, even after lifesaving fetal intervention and surgical correction. Therefore, an accurate prenatal diagnosis is necessary to give the couple an option of continuing pregnancy after realistic counseling regarding the prognosis and postnatal outcome.

Congenitally Corrected Transposition of the Great Arteries in Utero: Morphological Spectrum, Outcomes and Pitfalls in Fetal Diagnosis.

Congenitally corrected transposition of the great arteries (ccTGA) is a rare malformation with diverse morphology. We assessed features of fetuses with ccTGA and evaluated neonatal and pediatric outcomes. This was a retrospective review of fetuses with ccTGA at Birmingham Women's and Children's Hospital born from 2005 to 2019. Of thirty-six fetuses identified, six had unavailable prenatal data, one was postnatally diagnosed with isomerism and 29 fetuses were evaluated. ccTGA without associated cardiac lesions was found in 28% (8/29), ccTGA with significant VSD in 31% (9/29), ccTGA with pulmonary obstruction in 24% (7/29) and ccTGA with complex anomalies in 17% (5/29). Tricuspid regurgitation (TR) was observed in 17% (5/29) and heart block (HB) in 10% (3/29) prenatally. Six, that is 21% underwent genetic testing of which one was abnormal. Five extra-cardiac anomalies were reported prenatally and postnatally. Pregnancy was discontinued in five, of which two had moderate TR. There were thirty-one liveborn. Coarctation of the aorta was found in five postnatally but not suspected prenatally. In one, pulmonary stenosis was underestimated; otherwise, prenatal morphology was confirmed. Cardiac interventions were performed in 77% (24/31) liveborn with 39% (12/31) undergoing neonatal intervention. Overall, 6/31 liveborn died including all three with prenatal heart block and one with TR. Estimated survival for all liveborn at 1, 5 and 10years was 87% (95% CI 76-100%), 83% (95% CI 72-98%) and 80% (95% CI 66-96%) respectively. Accurate prenatal diagnosis of ccTGA is critical for counseling. Early outcomes are favorable with 77% of liveborn undergoing surgery. Fetuses with prenatal diagnosis of complex associated abnormalities, HB and TR appear to do less well.

Innovative cardiovascular casting technique features the complex malformation of berry syndrome

BackgroundPrenatal diagnosis of Berry syndrome, a rare combination of cardiac anomalies including aortopulmonary window (APW), aortic origin of the right pulmonary artery (RPA), interrupted aortic arch (IAA), hypoplastic aortic arch, or coarctation of the aorta (COA), poses a significant challenge. Due to the rarity of the disease, and the limited case reports available to features the complex malformation of Berry syndrome postpartum, this article introduces an innovative approach to visually showcase this unusual disease. The proposed method provides a comprehensive display of the structural deformities, offering valuable insights for clinical practitioners seeking to comprehend this condition.Case presentationIn this report, we present a case where fetal echocardiography aided in diagnosing Berry syndrome, which was later confirmed through postpartum cardiovascular casting. Our experience highlights the importance of using the three-vessel view to diagnose APW and aortic origin of the right pulmonary artery. Additionally, obtaining true cross-sectional and sagittal views by continuously scanning from the three-vessel-trachea view to the long-axis view of the aortic arch is necessary to image IAA or coarctation of the aortic arch.ConclusionsEarly and accurate prenatal diagnosis of Berry syndrome is feasible and our cardiovascular cast can perfectly display the microvascular morphology of the fetal heart, which may have great application prospects for postpartum diagnosis and teaching of complex cardiac abnormalities.

Prenatal transposition of great arteries diagnosis and management: a Chinese single-center study.

This study aimed to assess the diagnostic value of prenatal echocardiography for identifying transposition of the great arteries (TGA) during pregnancy and evaluating the associated outcomes. We conducted a retrospective analysis of 121 prenatally diagnosed patients with TGA at our hospital between January 2012 and September 2022. This analysis included prenatal ultrasound, prenatal screening, clinical management and follow-up procedures. Among the 103 fetuses considered in the study, 90 (87.4%) were diagnosed with complete transposition of the great arteries (D-TGA), while 13 (12.6%) exhibited corrected transposition of the great arteries (CC-TGA). Diagnoses were distributed across the trimester, with 8 D-TGA and 2 CC-TGA patients identified in the first trimester, 68 D-TGA patients and 9 CC-TGA patients in the second trimester, and 14 D-TGA and 2 CC-TGA patients referred for diagnosis in the third trimester. Induction of labour was pursued for 76 D-TGA patients (84.4%) and 11 CC-TGA patients (84.6%), and 14 D-TGA patients (15.6%) and 2 CC-TGA patients (15.4%) continued pregnancy until delivery. Among the D-TGA patients, 9 fetuses (10.0%) underwent surgery, two of which were inadvertent fatality, while the remaining seven experienced positive outcomes. Additionally, seven TGA patients received palliative care, leading to four fatalities among D-TGA patients (5.2%), whereas 1 D-TGA patients and 2 CC-TGA patients survived. This study underscores the feasibility of achieving an accurate prenatal diagnosis of TGA during early pregnancy. The utility of prenatal ultrasound in the development of personalized perinatal plans and the application of multidisciplinary treatment during delivery are conducive.

Case Report: Thanatophoric dysplasia

Thanatophoric dysplasia (TD) is a rare and lethal skeletal dysplasia caused by a de novo mutation in the fibroblast growth factor receptor 3 gene (FGFR3), with a frequency range of 1 in 20,000 to 50,000. We report a case of a 19-year-old primigravida from rural Nepal who presented with ultrasonographic findings suggestive of TD at 26 weeks and three days of gestation. The pregnancy was terminated due to the lethal nature of the condition. Accurate prenatal diagnosis and comprehensive counselling are paramount for families affected by this condition. This case has been reported due to its rarity, with the aim of raising awareness among healthcare professionals about this devastating condition.

ABDOMINAL WALL DEFECTS: GASTROSCHISIS, DEFINITION, EPIDEMIOLOGY, PATHOGENESIS, TYPES, DIAGNOSIS AND MANAGEMENT

Introduction: Abdominal wall defects are common congenital anomalies, both gastroschisis and omphalocele conform to fetal developmental anomalies that favor multidisciplinary support before and after birth. Outcomes for newborns with gastroschisis usually depend on the distinctive features of the abdominal wall defect and underlying intestinal viability, whereas omphalocele outcomes are determined by the size of the defect and the presence of other related anomalies. Objective: to detail current information related to the two fetal abdominal wall defects, especially gastroschisis definition, epidemiology, pathogenesis, types, diagnosis and management. Methodology: a total of 48 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 36 bibliographies were used because the other articles were not relevant to this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: fetal abdominal wall defects, gastroschisis, prenatal anomalies, surgery and prosthetic silo. Results: The incidence of gastroschisis ranges from 0.4 to 3 per 10,000 births and shows an upward pattern, the incidence of omphalocele ranges from 1.5 to 3 per 10,000 births. About 10% of infants with gastroschisis have intestinal stenosis or atresia because of vascular insufficiency due to volvulus or compression of the vascular pedicle by a narrowing abdominal ring. Periconceptional genitourinary tract infections were significantly associated with gastroschisis (OR, 1.5; 95 % CI, 1.3 to 1.9). Other significant associations presented in various studies with gastroschisis pregnancies include smoking (odds ratio (OR), 2.86; 95 % CI, 2.22-3.66), history of pregestational or gestational diabetes (OR, 2.81; 95 % CI, 1.42-5.5), and use of antidepressant medications (OR, 4.4; 95 % CI, 1.38-11.8). Conclusions: Abdominal wall defects are common congenital anomalies, both gastroschisis and omphalocele represent different embryological outcomes, which depend on accurate prenatal diagnosis and referral to a multidisciplinary fetal center. Gastroschisis is a congenital anomaly of the rudimentary umbilical ring, in which there is herniation of a variable portion of viscera through the defect, with no membrane or covering sac, and its prevalence has been steadily increasing. Gastroschisis is classified into simple and complex types. Prenatal ultrasound scans can diagnose gastroschisis as early as 12 weeks of gestation. Routine preterm delivery or elective cesarean section has not been shown to improve outcome. Surgical management after birth is aimed at reduction of the herniated viscera and closure of the abdominal wall. Survival rates are usually high; however, the prognosis depends on the state of the bowel at birth. Those affected with significant intestinal alteration at birth are at higher risk of premature death or later complications. Future fetal surgery could improve the outlook and management of the condition. KEY WORDS: gastroschisis, abdominal wall defect, congenital.

Prenatal diagnosis of 1408 foetuses at risk of DMD/BMD by MLPA and Sanger sequencing combined with STR linkage analysis

ObjectiveThis study is a retrospective analysis of the prenatal genetic diagnosis results of 1408 foetuses at high risk of DMD/BMD to provide information for clinical genetic counselling.BackgroundDuchenne muscular dystrophy (DMD) is a severe neuromuscular disorder characterized by skeletal and cardiac muscle weakness. With the deepening of disease research, some treatments have been applied in clinics. Therefore, early and accurate prenatal diagnosis can inform pregnancy choices for high-risk families.MethodsA total of 1316 unrelated DMD/BMD families with confirmed genetic diagnoses were recruited from the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University. Prenatal diagnosis of 1408 high-risk foetuses was performed by MLPA and Sanger sequencing combined with STR linkage analysis for all families.ResultsAmong the 1316 families, large deletions, duplications, and small variants of the DMD gene accounted for 70.4% (927/1316), 8.2% (108/1316), and 21.4% (281/1316), respectively. Among 1316 mothers, 863 (65.6%) were carriers, and 453 (34.4%) were not carriers. The rate of de novo variants was 34.4% (453/1316) in our study. In addition, gonadal mosaicism was observed in 11 pregnant females. Prenatal diagnosis was provided for 1408 high-risk foetuses; 282 foetuses were identified as male patients, 219 foetuses were female carriers, and the remainder had normal genetics. The results of prenatal diagnosis were consistent with the results of follow-up.ConclusionsAccurate and rapid prenatal diagnosis can be achieved using MLPA, Sanger sequencing, and STR linkage analysis. Furthermore, germline mosaicism in DMD should not be ignored; considering this, a prenatal diagnosis for all pregnant women with a family history of DMD/BMD regardless of whether they carried disease-causing variants is proposed. Genetic counselling and targeted prenatal diagnosis will continue to be a cornerstone of DMD/BMD family management in the future.

Functional analysis of a novel splice site variant in the ASAH1 gene.

Acid ceramidase (ACDase) deficiency is an ultrarare autosomal recessive lysosomal disorder caused by pathogenic N-acylsphingosine amidohydrolase (ASAH1) variants. It presents with either Farber disease (FD) or spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). The study aims to identify a novel splice site variant in a hydrops fetus that causes ASAH1-related disorder, aid genetic counseling, and accurate prenatal diagnosis. We report a case of hydrops fetalis with a novel homozygous mutation in ASAH1 inherited from non-consanguineous parents. We performed copy number variation sequencing (CNV-Seq) and whole exome sequencing (WES) on the fetus and family, respectively. Minigene splicing analyses were conducted to confirm the pathogenic variants. WES data revealed a splice site variant of the ASAH1 (c.458-2A>T), which was predicted to affect RNA splicing. Minigene splicing analyses found that the c.458-2A>T variant abolished the canonical splicing of intron 6, thereby activating two cryptic splicing products (c.456_458ins56bp and c.458_503del). Overall, we identified a novel splice site variant in the mutational spectrum of ASAH1 and its aberrant effect on splicing. These findings highlight the importance of ultrasonic manifestation and family history of fetal hydrops during ASAH1-related disorders and could also aid genetic counseling and accurate prenatal diagnosis. To the best of our knowledge, this is the shortest-lived account of ASAH1-related disorders in utero with severe hydrops fetalis.