Accurate Prenatal Diagnosis Research Articles

Prenatal diagnosis of a fetus with 46,XX (SRY positive) male syndrome

To carry out genetic testing for a XXY fetus suggested by non-invasive prenatal testing (NIPT). G-banding karyotyping, fluorescence in situ hybridization (FISH) and chromosomal microarray analysis (CMA) were performed on amniocytes from the fetus. The genitalia of the fetus was also examined by Doppler ultrasonography. The result was verified with peripheral blood samples from its parents and a brother. The fetus was found to have a 46,XX karyotype. CMA showed presence of sequences from Yp11.2 (2.635 Mb) and Yp11.31p11.2 (3.706 Mb). FISH assay suggested that the SRY fragment on Yp has translocated to Xpter. No karyotypic or pathogenic CNVs was detected in its parents and brother. The fetus was ultimately diagnosed with 46,XX (SRY positive) male syndrome. The combination of G-banding karyotyping, FISH, and CMA is of great significance for attaining accurate prenatal diagnosis for this fetus.

The novel mutation in the COL7A1 gene in the patient with dystrophic forms of epidermolysis bullosa

Dystrophic Epidermolysis Bullosa (DEB) is a rare inherited blistering disorder with both autosomal recessive (RDEB) and autosomal dominant (DDEB) mode of inheritance. DEB is characterized by affected dermis-epidermis conjunction, which results from COL7A1 mutations. COL7A1 encodes collagen VII, the major component of anchoring fibrils (AF), which is responsible for dermis-epidermis conjunction. Structural modification of AFs or significant alterations in its numbers could result in DEB. In the current investigation, patients within six families affected by DEB underwent complete clinical evaluation. Moreover, the causative mutations were identified in the COL7A1 gene by next generation sequencing and then confirmed by Sanger sequencing. A pathogenic homozygous and heterozygous glycine substitution mutation were identified in exon 54 of twin siblings of the family I (c.5018G > A, p.G1673E). In family II, a frameshift deletion mutation in exon 75 was identified in a 7-year-old patient (c.6265delC, p.P2090fs). A novel pathogenic frameshift insertion mutation was confirmed in a 6-year-old girl (c.179-180insGAAA, p.F60fs) in family III. These findings expand scientific knowledge of the EB causative mutations, which facilitates the EB classification and lead to more accurate prenatal diagnosis in the families at the high risk of such diseases.

Nonketotic Hyperglycinemia in Tunisia. Report upon a Series of 69 Patients.

The aim of the study is to report on epidemiological, clinical, and biochemical characteristics of nonketotic hyperglycinemia (NKH) in Tunisia. Patients diagnosed with NKH in Laboratory of Biochemistry at Rabta hospital (Tunis, Tunisia) between 1999 and 2018 were included. Plasma and cerebrospinal fluid (CSF) free amino acids were assessed by ion exchange chromatography. Diagnosis was based on family history, patient's clinical presentation and course, and increased CSF to plasma glycine ratio. During 20 years, 69 patients were diagnosed with NKH, with 25 patients originating from Kairouan region. Estimated incidences were 1:55,641 in Tunisia and 1:9,684 in Kairouan. Consanguinity was found for 73.9% of the patients and 42% of the families have history of infantile death due to a disease of similar clinical course than the propositus. Clinical symptoms initiated within the first week of life in 75% of the patients and within the first 3 months in 95.7% ones. The phenotype was severe in 76.8% of the patients. Main symptoms were hypotonia, feeding difficulties, coma, apnea, and seizures. Most patients died within few days to months following diagnosis. CSF to plasma glycine ratio was increased in all patients. CSF and plasma glycine levels were negatively correlated with age of disease onset and severity. NKH is quite frequent in Tunisia. Kairouan region has the highest NKH incidence rate, worldwide. However, due to lack of confirmatory enzymatic and genetic tests, NKH diagnosis was based on first-line biochemical tests. Characterization of causal mutations is needed for accurate diagnosis and prenatal diagnosis of this devastating life-threatening disease.

Genetic study of a trisomy 13 fetus with a false-negative karyotype by chorionic villi analysis

To explore the mechanism of a false-negative result from karyotyping of chorionic villi cells for a trisomy 13 fetus featuring multiple malformations. For a fetus with multiple malformations by ultrasonography and a 46,XY karyotype by chorionic villi analysis, amniocytes were further analyzed with quantitative fluorescence PCR (QF-PCR), G-banded karyotyping and chromosomal microarray analysis (CMA). Meanwhile, non-invasive prenatal testing (NIPT) was conducted on peripheral blood sample from the pregnant woman to determine the chromosomal composition of cytotrophoblast. After induction of labor, common aneuploidies in placenta and fetal tissue were also analyzed by QF-PCR. QF-PCR, chromosomal karyotyping and CMA analysis of the amniocytes all suggested complete trisomy 13 (47,XY,+13) in the fetus. NIPT also suggested existence of fetal trisomy 13. QF-PCR analysis of the placenta and fetal tissues revealed that cells derived from the maternal surface and right side of fetal surface harbored mosaic trisomy 13, while those derived from other sites of fetal surface of the placenta, umbilical cord, amniotic membrane and fetal muscle tissue harbored trisomy 13. Karyotyping of long-term cultured chorionic villus sample may give rise to false negative results due to placental mosaicism. To ensure accurate prenatal diagnosis, discordance between karyotyping of chorionic villi cells, fetal ultrasound and NIPT result should be verified by amniocentesis or cordocentesis and application of multiple cytogenetic and molecular techniques.

Current Perspectives of Prenatal Sonographic Diagnosis and Clinical Management Challenges of Nuchal Cord(s).

Umbilical cord accidents preceding labor are uncommon. In contrast, nuchal cords are a very common finding at delivery, with reported incidences of a single nuchal cord of approximately between 20% and 35% of all singleton deliveries at term. Multiple loops occur less frequently, with reported incidence rates inverse to the number of nuchal cords involved. Rare cases of up to 10 loops of nuchal cord have been reported. While true knots of the umbilical cord have been associated with a 4–10-fold increased risk of stillbirth, nuchal cord(s) are most often noted at delivery of non-hypoxic non-acidotic newborns, without any evidence of subsequent adverse neonatal outcome. Prior to ultrasound, nuchal cords were suspected clinically following subtle (spontaneous or evoked) electronic fetal heart rate changes. Prenatal sonographic diagnosis, initially limited to real-time gray-scale ultrasound, currently entails additional sonographic modalities, including color Doppler, power Doppler, and three-dimensional sonography, which have enabled increasingly more accurate prenatal sonographic diagnoses of nuchal cord(s). In contrast to true knots of the umbilical cord (which are often missed at sonography, reflecting the inability to visualize the entire umbilical cord, and hence are often incidental findings at delivery), nuchal cord(s), reflecting their well-defined and sonographically accessible anatomical location (the fetal neck), lend themselves with relative ease to prenatal sonographic diagnosis, with increasingly high sensitivity and specificity rates. While current literature supports that single (and possibly double) nuchal cords are not associated with increased adverse perinatal outcome, emerging literature suggests that cases of ≥3 loops of nuchal cords or in the presence of a coexisting true knot of the umbilicus may be associated with an increased risk of stillbirth or compromised neonatal status at delivery. This commentary will address current perspectives of prenatal sonographic diagnosis and clinical management challenges associated with nuchal cord(s) in singleton pregnancies.

Identification of two rare mutations c.1318G>A and c.6438+2T>G in a Chinese DMD family as genetic markers.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disorder with no effective treatment, which underscores the importance of avoiding the birth of children with DMD by identifying pathogenic mutations and obtaining an accurate prenatal diagnosis. The objective of this study was to analyze the genetic defect of a Chinese family where all male patients have died of DMD. Multiplex ligation dependent probe analysis (MLPA) and next-generation sequencing (NGS) were employed to detect DMD mutations. The candidate mutations were then validated by Sanger sequencing. In vitro splicing assay was further conducted to examine the potential effect of the novel DMD splice site mutation on splicing. We found that two rare DMD mutations c.1318G>A and c.6438+2T>G passed from generation to generation among female carriers and they may be used as genetic markers in the Chinese DMD family. In vitro splicing assay further revealed that the novel classical splice site mutation c.6438+2T>G gave rise to a new donor splice site, which resulted in a frame shift of the transcripts and a premature termination at position 2159 in exon 45 (p.Y2144Nfs*16). We found that two co-inherited mutations passed from generation to generation in female carriers and they may be used as genetic markers in the Chinese DMD family. Our findings not only expanded the DMD mutation spectrum, but also provided an important basis for identifying of female carriers and avoiding the birth of affected male children in this DMD family.

A Review on Holoprosencephaly Disease (CYCLOPIA): Risk Factors, Causes, Pathophysiology and Diagnosis with spotlight of various features reported in cases

Holoprosencephaly has a sever condition called Cylopia that is occur due to embryonic prosencephalon cleavage failure and contrast. Mostly cylopia form is holoprosencephaly, mid facial tissue is absent which causes the one eye on a single orbit. It is a sever deformity of median faciocerebal development. There are 1.05 cases in100,000 birth, still births of cyclopean. Abnormal nose above eyes or absence of nose, single eyes or half divided eyes in single orbit are features of cyclopia, where as reduced size of oral aperture or absence of mouth, absence of mandible with ears below chin. It is as etiologically heterogeneous condition, which can be caused by genetic mutation, chromosomal defect and teratogenic environmental factors. Environmental factors can be diabetic embryopathy, retinoic acid, several anecdotal suggestion of teratogenic factor for HPE, which includes salicylates and viruses. Some list of syndrome are also involved to cause cyclopia Like steinfeld syndrome, dysgnathia complex,Pseudotrisomy 13 syndrome and Smith–Lemli– Opitz syndrome. On other hand inborn abnormalities also cause cyclopia but its come under chromosomal syndrome. Anatomical detection can be done by brain MRI, whereas in prenetal diagnosis, sonography is more significant. Ultrasound also used early detection can be done and knowledge of sonographic finding soectrum leads to accuracy of prenatal diagnosis of cyclopia. After birth the chromosomal study helps to diagnose cyclopia along with postmortem biopsy.

Development of DNA controls for detection of β-thalassemia mutations commonly found in Asian.

Several DNA-based approaches including a reverse dot-blot hybridization (RDB) have been established for detection of β-thalassemia genotypes to provide accurate genetic counseling and prenatal diagnosis for prevention and control of severe β-thalassemia. However, one of major concerns of these techniques is a risk of misdiagnosis due to a lack of DNA controls. Here, we constructed positive DNA controls for β-thalassemia genotyping in order to ensure that all steps in the analysis are performed properly. Four recombinant β-globin plasmids, including a normal sequence and three different mutant panels covering 10 common β-thalassemia mutations in Asia, were constructed by a conventional cloning method followed by sequential rounds of site-directed mutagenesis. These positive DNA controls were further validated by RDB analysis. We demonstrated the applicability of established positive DNA controls for β-thalassemia genotyping in terms of accuracy and reproducibility by RDB analysis. We further combined three mutant β-globin plasmids into a single positive control, which showed positive signals for both normal and mutant probes of all tested mutations. Therefore, only two positive DNA controls, normal and combined mutant β-globin plasmids, are required for detecting 10 common β-thalassemia mutations by RDB, reducing the cost, time, and efforts in the routine diagnosis. The β-globin DNA controls established here provide efficient alternatives to a conventional DNA source from peripheral blood, which is more difficult to obtain. They also provide a platform for future development of β-globin plasmid controls with other mutations, which can also be suitable for other DNA-based approaches.

A novel splice-site mutation in the LRP5 gene causing Familial Exudative Vitreoretinopathy

Familial Exudative Vitreoretinopathy (FEVR) is an inherited heterogeneous eye disorder in children that can be caused by mutations in the LRP5 gene with autosomal dominant or recessive mode of inheritance. Patients might show variable clinical features ranging from few or no visual problems to early-onset blindness. Mutations which lead to loss or gain of function in the LRP5 gene, can affect vascularization, bone density or both. In this investigation we report two children (8-year-old girl and 6-year-old boy) with severe type of FEVR from unrelated families. Both patients presented with bilateral blindness and reduced Bone Mineral Density. Next generation sequencing was used to identify the causative mutation, which revealed a novel homozygous splice-site mutation (NM_002335.4: c.686+1G>T) in the LRP5 gene in our patients. Sanger sequencing was carried out to validate the NGS result in our patients and their families that confirmed the autosomal recessive inheritance pattern in these families. Moreover, q-Real Time PCR was conducted to quantify the mRNA expression level of LRP5 gene in patients and their family members, which revealed nearly the full decrease in the LRP5 expression level in patients and around 50% decrease in the carriers of mutation compared to controls that strongly suggesting the pathogenicity of the identified mutation. Current study identified a novel pathogenic homozygous splice-site mutation in the LRP5 gene and confirms this gene's involvement in an autosomal recessive FEVR (severe form), therefore it can help to conduct an accurate genetic counseling and prenatal diagnosis for high risk families.

Telediagnosis system for congenital heart disease in a Japanese prefecture.

This study aimed to evaluate the accuracy of prenatal diagnosis using a spatio-temporal image correlation-based telediagnosis system at a tertiary referral unit in a Japanese prefecture over a 9-year period, and to investigate the validity of delivery hospital selection. This study retrospectively analyzed telediagnosis cases from 2009 to 2018 in six geographically remote hospitals. We built a telediagnosis system called the Kyoto Fetal Ultrasonographic Telediagnosis System (K-FUTS). Three-dimensional ultrasonographic images from these referral hospitals were forwarded to the Kyoto Prefectural University of Medicine (KPUM) Hospital through an optical fiber network system for analysis. The primary endpoint was accuracy of prenatal diagnosis. Cases with severe congenital heart disease (CHD) that required immediate postnatal treatment were identified using the K-FUTS. These cases were then examined to determine whether they were delivered at appropriate hospitals. During the study period, datasets from 182 cases were transferred to KPUM Hospital. Twenty-one datasets were excluded because of data unavailability or poor image quality. CHD was detected in 14.9% of cases (24/161); the accuracy of prenatal diagnosis was 95.0% (153/161). The K-FUTS identified seven severe cases with CHD requiring immediate postnatal surgical or medical treatment. These cases were delivered at KPUM Hospital with a pediatrician present. The remaining 17 cases considered suitable for delivery at the referral hospitals were delivered there, and they did not require intervention immediately after birth. Our telediagnosis system contributed to the prenatal diagnosis of CHD and management of pregnancies in patients who were geographically remote from a tertiary hospital.

Congenital pancreatic pseudocyst

Abstract Pancreatic pseudocysts (PPs) rarely occur in the fetus. Accurate prenatal diagnosis is challenging. We report a case of left upper abdominal cystic mass detected by prenatal ultrasonography and Magnetic resonance imaging (MRI), which finally proven PPs histologically after birth. Operative interventions include complete pseudocystectomy and subsequent external drainage. The outcome is satisfactory.

Current Perspectives of Prenatal Sonographic Diagnosis and Clinical Management Challenges of True Knot of the Umbilical Cord.

Umbilical cord accidents preceding labor are rare. Single and multiple nuchal cords, and true knot(s) of the umbilical cord, are often incidental findings noted at delivery of non-hypoxic non-acidotic newborns without any evidence of subsequent adverse neonatal outcome. In contrast to single nuchal cords, true knots of the umbilical cord, which occur in between 0.04% and 3% of all deliveries, have been associated with a reported 4 to 10 fold increased risk of stillbirth. First reported with real-time ultrasound, current widespread application of color Doppler, power Doppler and three-dimension sonography, has enabled increasingly more accurate prenatal sonographic diagnoses of true knot(s) of the umbilical cord. Reflecting the inability to visualize the entire umbilical cord at prenatal ultrasound assessment, despite detailed second and third-trimester scanning, many occurrences of incidental true knot of the umbilical cord remain undetected and are noted only at delivery. Although prenatal sonographic diagnostic accuracy is increasing, false positive sonographic diagnosis of true knot of the umbilical cord cannot be ruled out with certainty, and must continue to be considered clinically. Notwithstanding the inability to diagnose all true knots, currently there is a clear absence of clinical management guidelines by governing bodies regarding patients in whom prenatal sonographic diagnosis of true knot(s) of the umbilical cord is / are suspected. As a result, in many prenatal ultrasound units, suspected sonographic findings suggestive of or consistent with true knot of the umbilical cord are often disregarded, not documented, and patients are not uniformly informed of this potentially life-threatening condition, which carries an associated considerable risk of stillbirth. This commentary will address current perspectives of prenatal sonographic diagnostic and management challenges associated with true knot(s) of the umbilical cord in singleton pregnancies.

Special statement: Proposed quality metrics to assess accuracy of prenatal detection of congenital heart defects

Congenital heart defects are a leading cause of neonatal morbidity and mortality. Accurate prenatal diagnosis of congenital heart defects can reduce morbidity and mortality by improving prenatal care, facilitating predelivery pediatric cardiology consultation, and directing delivery to facilities with resources to manage the complex medical and surgical needs of newborns with congenital heart defects. Unfortunately, less than one half of congenital heart defect cases are detected prenatally, resulting in lost opportunities for counseling, shared decision-making, and delivery at an appropriate facility. Quality improvement initiatives to improve prenatal congenital heart defects detection depend on the ability to measure the rate of detection at the level of providers, facilities, or populations, but no standard metric exists for measuring the detection of congenital heart defects at any level. The need for such a metric was recognized at a Cooperative Workshop held at the 2016 Annual Meeting of the Society for Maternal-Fetal Medicine, which recommended the development of a quality metric to assess the rate of prenatal detection of clinically significant congenital heart defects. In this paper, we propose potential quality metrics to measure prenatal detection of critical congenital heart defects, defined as defects with a high rate of morbidity or mortality or that require surgery or tertiary follow-up. One metric is based on a retrospective approach, assessing whether postnatally diagnosed congenital heart defects had been identified prenatally. Other metrics are based on a prospective approach, assessing the sensitivity and specificity of prenatal diagnosis of congenital heart defects by comparing prenatal ultrasound findings with newborn findings. Potential applications, limitations, challenges, barriers, and value for both approaches are discussed. We conclude that future development of these metrics will depend on an expansion of the International Classification of Diseases system to include specific codes that distinguish fetal congenital heart defects from newborn congenital heart defects and on the development of record systems that facilitate the linkage of fetal records (in the maternal chart) with newborn records.

AIUM Practice Parameter for the Performance of Fetal Echocardiography.

AIUM Practice Parameter for the Performance of Fetal Echocardiography.

A novel ATRX mutation causes Smith‑Fineman‑Myers syndrome in a Chinese family.

Smith‑Fineman‑Myers syndrome (SFMS) is a rare inherited disorder characterized mainly by mental retardation and anomalies in the appearance of patients. SFMS is caused by a mutation in the α‑thalassemia/mental retardation syndrome X‑linked (ATRX) gene and has an X‑linked recessive pattern. In the present study, a novel ATRX mutation was identified, and the association between its genotype and the phenotype was explored in a Chinese Han family with SFMS. This study aimed to lay a foundation for prenatal diagnosis for this family. Briefly, genomic DNA was extracted from peripheral blood samples obtained from the family. High‑throughput genetic sequencing was employed to detect the whole exome; subsequently, Sanger sequencing was performed to verify the candidate mutations. Clinical analysis of the proband was also accomplished. Consequently, a novel missense ATRX mutation was identified comprising a single nucleotide change of CtoT, which caused an amino acid substitution at codon 172 in exon7 (c.515C>T; p.Thr172Ile) of the proband. This mutation was found to co‑segregate in the present SFMS pedigree and was located in a highly conserved region of the ATRX protein, thus suggesting that it may be a pathogenic mutation. Taken together, these findings provided novel information that may lead towards an improved understanding of the genetic and clinical features of patients with SFMS, thereby facilitating a more accurate prenatal diagnosis of SFMS.

Accurate Prenatal Diagnosis of Cleft Palate Using Magnetic Resonance Imaging with Slice-to-Volume Reconstruction

Cleft palate (CP) is one of the most common human birth defects. The routine clinical technique for prenatal diagnosis of CP is ultrasound (US). However, US has many limitations on the diagnosis of CP especially posterior CP. In this work, we employed a 3D super-resolution reconstruction method to reconstruct 3D isotropic volumetric images from a series of 2D images and evaluate its feasibility to the diagnosis of CP. Quantitative comparison between original 2D and the reconstructed 3D images shows that the reconstructed 3D images have better image quality than the original 2D images in terms of SNR (21.48 ± 0.58 vs. 14.80 ± 2.59, p = 0.021), CNR (73.13 ± 10.96 vs. 42.97 ± 6.75, p = 0.022), image quality score (3.4 ± 0.7 vs. 3.0 ± 0.8, p = 0.046), and diagnostic confidence score (3.8 ± 0.4 vs. 3.1 ± 0.9, p = 0.038). Using the findings at birth as standard reference, the sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV), and the accuracy (ACC) of conventional 2D method and the proposed 3D method were calculated, and all participants were correctly identified by the radiologists based on the reconstructed 3D images. There was one participant with fetal cleft lip and palate that were not correctly identified based the original 2D images. Therefore, the reconstructed 3D images can improve the accuracy and efficiency of the prenatal diagnosis of CP. It can serve as a complementary tool for the diagnosis of CP.

Compound heterozygous variants in MYH11 underlie autosomal recessive megacystis-microcolon-intestinal hypoperistalsis syndrome in a Chinese family

Megacystis-microcolon-intestinal-hypoperistalsis syndrome (MMIHS) is a rare and severe disorder characterized by functional obstruction in the urinary and gastrointestinal tract. The molecular basis of this condition has been defined recently. Heterozygous variants in ACTG2, homozygous mutations in LMOD1, MYLK, and MYH9 were related to the pathogenesis of the syndrome, which encodes proteins involved in the process of smooth muscle contraction, supporting a myopathic basis for the disease. Recent studies have identified homozygous or compound heterozygous variants in MYH11 as a candidate gene of MMIHS. In this report, we described a nonconsanguineous Chinese family with three male fetuses affected with megacystis. Trio-targeted exome sequencing identified compound heterozygous variants, c.2051 G > A (p.R684H) and c.3540_3541delinsTT (p.(E1180D, Q1181Ter)), in MYH11 (NM_001040114). The variants were inherited from the parents, respectively. Western blotting showed a marked decrease in MYH11 protein in the proband’s umbilical cord tissue compared with the control sample. The study’s results confirmed that MYH11 is a candidate gene for MMIHS with autosomal recessive (AR) inheritance and expanded the mutation spectrum for this clinical condition. Combining clinical phenotype with molecular diagnosis may enable the identification of candidate genes for potential monogenic diseases and facilitate accurate genetic counseling, informed decision-making, and prenatal diagnosis.

Prenatal diagnosis of a fetus with Phelan-McDermid syndrome

To diagnose a fetus with Phelan-McDermid syndrome (PMS) using various techniques. Single nucleotide polymorphism array (SNP Array), multiplex ligation-dependent probe amplification (MLPA), fluorescence in situ hybridization (FISH) were applied in conjunction for the prenatal diagnosis of the fetus. SNP Array detected a 4.03 Mb microdeletion at 22q13.31q13.33 in the fetus, which was confirmed by FISH and MLPA. FISH analysis of the parents suggested that the 22q13.31q13.33 deletion has a de novo origin. Combined use of various techniques can enable accurate prenatal diagnosis and genetic counseling.

Prenatal diagnosis of unilateral absence of pulmonary artery by echocardiography

Objective To analyze the echocardiography features of unilateral absence of pulmonary artery (UAPA) features and improve the prenatal diagnosis accuracy of UAPA by analyzing fetal echocardiography features. Methods Fetal echocardiographic features were analyzed retrospectively in 6 cases with prenatal diagnosis of UAPA between June 2012 and October 2018. At the same time, ultrasonic manifestations of 3 patients whose antenatal examinations were performed in other hospitals and diagnosed as UAPA in our hospital were retrospectively analyzed. The fetal echocardiography characteristics of UAPA were summarized. Results Among the 6 fetuses with UAPA, 4 cases were diagnosed as isolated unilateral absence of proximal right pulmonary artery, 1 was unilateral absence of proximal left pulmonary artery with tetralogy of Fallot (TOF) and 1 was isolated unilateral absence of proximal left pulmonary artery. Characteristic sonographical findings included: ①When other intracardiac abnormalities were absent, the inner diameter and proportion of the heart cavity was normal. ②Multi-view showed that the normal confluence structure disappeared at the branch of the main pulmonary artery, and the diameter of normal pulmonary artery branch was widened. ③On the basis of three vessels and trachea view (3VT), moved the probe up and down to make a transverse scan, two-dimensional and color Doppler flow imaging (CDFI) showed a large vessel (the brachiocephalic trunk artery) originating from the aortic arch which had dual vascular features, it means that it was difficult to distinguish the pulmonary artery branch from the aortic branch. ④On coronal view of the large vessel, two-dimensional and CDFI clearly showed that the large vessel originating from the aortic arch was the brachiocephalic trunk artery, and the pulmonary artery branch connected with the brachiocephalic trunk artery by the ipsilateral vertical arterial duct (DA) which originated from the root of brachiocephalic trunk artery, but the left pulmonary artery branch connected with the ventral side of the aortic arch by the left DA in UAPA fetus with TOF. ⑤Spectrum Doppler of the anomalous vessels of the lungs confirmed that it was the pulmonary artery, and the blood flow of the anomalous PA branch was isolated and no exact connection with the main pulmonary artery. Conclusions UAPA can be accurately diagnosed prenatally by echocardiography. The brachiocephalic trunk artery coronary view is very important for the diagnosis of this disease.Early diagnosis plays an important role in prenatal counseling and prognosis assessment. Key words: Echocardiography; Fetus; Unilateral absence of pulmonarya; Tetralogy of fallot

A sonographic approach to the prenatal diagnosis of skeletal dysplasias.

Skeletal dysplasias are a heterogeneous group of conditions, many of which present unexpectedly in the prenatal period with a variety of ultrasound findings. Accurate prenatal diagnosis can now be facilitated using exome sequencing approaches, but in order to interpret results, accurate and detailed phenotyping is required. Here, we describe the sonographic approach to the prenatal diagnosis of skeletal abnormalities and illustrate how taking a systematic approach can facilitate diagnosis.