Prenatal Diagnosis Research Articles

MRI and placenta accreta: Keys for its interpretation in images, regarding a case

Introduction: Placenta accreta spectrum (PAS) refers to the abnormal adherence of the placental trophoblast to the uterine myometrium. Several conditions are associated with its development. Ultrasound is the imaging modality of choice for antenatal diagnosis. In cases of doubt, magnetic resonance (MR) plays a leading role, due to its high performance, and contributes to surgical planning. The final diagnosis is made in the surgery, with subsequent confirmation by pathology. The objective of this article is to present a case of placenta increta, focused on the imaging findings in magnetic resonance imaging (MRI). Case Report: We present a case of a 35-year-old woman with a history of 2 previous cesarean sections and chronic hypertension, who presented a 23-week pregnancy with obstetric ultrasound showing placenta accreta. An MRI was performed, and it showed signs of placenta accreta, with no evidence of transmural extension to adjacent organs. At 34 weeks, a cesarean section and hysterectomy were performed, with no evidence of bladder invasion. Conclusion: The diagnosis of PAS is made antenatal with ultrasound, but MRI has been used in some cases, with some characteristic features that every radiologist should know.

Diagnosis, Management and Outcome of Truncus Arteriosus Communis Diagnosed during Fetal Life-Cohort Study and Systematic Literature Review.

Background/Objectives: Truncus arteriosus communis (TAC) is a rare congenital heart defect characterized by a single arterial trunk that supplies systemic, pulmonary, and coronary circulations. This defect, constituting approximately 1-4% of congenital heart diseases, poses significant challenges in prenatal diagnosis, management, and postnatal outcomes. Methods: A retrospective analysis was conducted at the local tertiary referral center on cases of TAC diagnosed prenatally between 2019 and 2024. Additionally, a systematic literature review was performed to evaluate the accuracy of prenatal diagnostics and the presence of associated anomalies in fetuses with TAC and compare already published data with the local results. The review included studies that especially described the use of fetal echocardiography, the course and outcome of affected pregnancies, and subsequent management strategies. Results: The analysis of local prenatal diagnoses revealed 14 cases. Of the 11 neonates who survived to birth, the TAC diagnosis was confirmed in 7 instances. With all seven neonates undergoing surgery, the intention-to-treat survival rate was 86%, and the overall survival rate was 55%. By reviewing published case series, a total of 823 TAC cases were included in the analysis, of which 576 were diagnosed prenatally and 247 postnatally. The presence of associated cardiac and extracardiac manifestations as well as genetic anomalies was common, with a 22q11 microdeletion identified in 27% of tested cases. Conclusions: Advances in prenatal imaging and early diagnosis have enhanced the management of TAC, allowing for the detailed planning of delivery and immediate postnatal care in specialized centers. The frequent association with genetic syndromes underscores the importance of genetic counseling in managing TAC. An early surgical intervention remains crucial for improving long-term outcomes, although the condition is still associated with significant risks. Long-term follow-up studies are essential to monitor potential complications and guide future management strategies. Overall, a coordinated multidisciplinary approach from prenatal diagnosis to postnatal care is essential for improving outcomes for individuals with TAC.

Case Report: Hemoglobin Hasharon with Concurrent Alpha Thalassemia in a Patient with Maple Syrup Urine Disease

Abstract Hemoglobin Hasharon (Hb Hasharon) is an unstable hemoglobin variant stemming from a mutation in the alpha globin gene. This mutation involves the replacement of aspartic acid with histidine at position 47 of the alpha globin chain. Initially identified in 1967 in Israel, Hb Hasharon has since been sporadically reported in various populations, including in Italy, Greece, Germany, and among Latin Americans of Mediterranean descent. Only three English articles have reported several cases of the combined alpha thalassemia deletion and Hasharon mutation, all between 1978-1980. Notably, there has been no prior report of Hb Hasharon with concurrent alpha thalassemia in patients with maple syrup urine disease (MSUD). We hereby present the first case of Hb Hasharon with alpha thalassemia in a patient diagnosed with MSUD. This patient, a 16-month-old female, received a prenatal diagnosis of MSUD through amniocentesis, confirming homozygosity for a known pathogenic variant in DBT (c.75_76delAT, p.C26wfsX2). Prompt initiation of formula feeding has effectively controlled her MSUD. The patient was referred for further evaluation due to hemoglobin newborn screen showing hemoglobin A, Hb F and “variant hemoglobin”. Her parents denied any family history of hemoglobinopathy. Her complete blood count was predominantly normal except for mild microcytosis, with a mean corpuscular volume of 69.1 fl (normal range 70.0-86.0 fl). The patient didn’t exhibit neonatal jaundice or any other signs or symptoms of hemolysis. The reticulocyte count was also within normal limits. The hemoglobin electrophoresis results revealed a complex pattern, with 28.8% of an unknown hemoglobin between zone 4 and 5 on capillary zone electrophoresis (CZE) as well as a possible A2 variant in zone 1. High-performance liquid chromatography (HPLC) indicated a 29.1% peak at a retention time of 4.72 minutes, along with several smaller peaks, that were indicative of the degradation of the unstable unknown hemoglobin. Although the zones and retention time aligned with Hb Hasharon, the percentage differed from the expected range of 19-20% in CZE and 18-21% in HPLC for this variant, prompting the team to order alpha and beta globin sequencing tests. Beta globin gene complete sequencing yielded negative results, while the sequencing of alpha globin gene revealed that the patient carries one copy of the -alpha3.7 alpha-globin deletion and one copy of the c.142G>C (p.Asp48His) variant in the alpha2-globin (HBA2) gene, resulting in an -alpha/alpha2alpha1 genotype with Hb Hasharon. While Hb Hasharon is generally not clinically significant, its co-occurrence with alpha-thalassemia can lead to hemolytic anemia. In our patient, clinic and chemical parameters were predominantly within normal ranges, except for mild microcytosis. The potential interaction between MSUD and Hb Hasharon with concurrent alpha thalassemia remains unknown. Continued patient monitoring will enable us to evaluate whether these conditions may influence each other’s clinical and biochemical profiles.

A fetus with a mass in the oral cavity: a rare case of large oral immature teratoma

Abstract Introduction/Objective Oral teratoma is a rare congenital neoplastic lesion composed of variable amounts of all three germ cell layers, comprising 2-9% of all teratomas. Teratomas are classified into subtypes depending upon the presence of immature components. Sacrococcygeal and head and neck regions are the most common sites, with slight female predominance. Mortality increases if diagnosed in the fetal or neonatal period. Methods/Case Report We report a case of male fetus diagnosed radiologically as ultrasound at 20 weeks of gestation revealed abnormal facial characteristics. A huge lump protruding from face measuring 10.8 x 6.7 cm was observed. Grossly a grey-white, multilobulated lesion was seen with cystic spaces originating from midline soft palate. Histologically an immature teratoma comprising bone, skin adnexae, glandular tissue and immature neuroepithelial tissue was identified. The case was distinguished as immature teratoma of the oropharynx. Results (if a Case Study enter NA) NA Conclusion Prenatal diagnosis with modalities including ultrasound, MRI, alpha fetoprotein concentrations, fetoscopy and fetal karyotyping is possible in early pregnancy which can aid in risk stratification and planning therapeutic interventions. Delayed diagnosis and treatment increase the likelihood of malignant transformation. Intrapartum intubation and resection of the tumor at the time of the cesarean section has shown better outcomes. However, despite all efforts, survival rates are low.

The Efficacy of Naso-Alveolar Molding on Premaxilla Pushback and Dentoalveolar Changes in Patients With Bilateral Cleft Lip and Palate.

To evaluate the extent of naso-alveolar molding (NAM) in pushing the premaxilla posteriorly in patients with bilateral cleft lip and palate (BCLP). Naso-alveolar molding application in cleft lip and palate cases bridges the cleft gap and increases nasal tip projection. In BCLP, NAM potentially mobilizes the premaxilla posteriorly to allow tension-free primary lip closure. However, some patients with BCLP with NAM history still necessitate osteotomy during labioplasty, questioning the efficacy of NAM for BCLP management. This single-center retrospective study was conducted using medical records of nonsyndromic patients with BCLP. Twenty-six patients with BCLP were enrolled over a 5-year period with a history of NAM application before primary labioplasty. The changes in premaxilla width (P), anterior arch width (A), posterior arch width (R), and anteroposterior projection of the premaxilla (P'-A') were statistically analyzed at 2 time points: (1) at the start of NAM application (T1) and (2) after completion of NAM before surgery (T2). The average age at NAM initiation was 46.2 ± 40.4 days, and the average duration of NAM usage was 125.14 ± 62.94 days. A and P-A showed significant differences between T1 and T2 (P < 0.0001), whereas the rest did not show significant differences in value following NAM application (P > 0.05). Naso-alveolar molding successfully pushed back the premaxilla portion about 4.68 ± 2.83mm on average. Naso-alveolar molding can push back the premaxillary protrusion up to 5mm, which can serve as a cutoff point for the consideration of combined modalities. Prenatal diagnosis, counseling, and cleft education should be the benchmark in cleft centers to improve overall patient outcomes.

Hope pluralism in antenatal palliative care

When parents face the distressing news during pregnancy that their baby is affected by a serious medical condition that will likely lead to the baby’s death before or soon after...

Ethical problems of prenatal diagnosis

The progress made in the last decade in the field of fetal pathology diagnostics, through a common interdisciplinary work effort particularly between gynaecologists and geneticists, was evident from the above.

Prenatal Phenotypic Analysis of Branchio-Oto-Renal Spectrum Disorder Attributable to EYA1 Gene Pathogenic Variants and Systematic Literature Review.

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. 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. 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. 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.

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 foetus, a surgical patient

The 1970s saw a rapid growth of interest in the medical field in the prenatal diagnosis of congenital malformations. Among these, the incidence rate of pathology susceptible to surgical correction or otherwise requiring an operative act to allow survival or a satisfactory quality of life is much higher than is commonly thought.

Hierarchical Classification of Factors Associated With Noninvasive Prenatal Testing Failures and Its Impact on Pregnancy Outcomes

Abstract Objective To conduct a hierarchical classification analysis of the nonreportable results of noninvasive prenatal testing in an attempt to reduce failure rates and provide pregnant women with accurate information to alleviate their anxiety. Methods In this study, 30,039 singleton pregnancies who underwent noninvasive prenatal testing in a single center from May 2019 to April 2022 were collected, and 811 samples with initial noninvasive prenatal testing failure were retrospectively analyzed. Grouping was based on the reasons for initial test failure; tracking the noninvasive prenatal testing results and prenatal diagnosis results (if any) of the “z-scores in the gray area” group and analyzing the possible influencing factors of the “low fetal fraction” group in the pre-experimental and experimental period by using one-way analysis of variance, Mann-Whitney U test, and χ2 test; and tracking the pregnancy outcomes of the test failures samples to analyze the risk of perinatal complications and adverse pregnancy outcomes of the different types of test failures. Results None of the samples' initial nonresults because of z-scores in the gray area were ultimately found to have chromosomal aneuploidy. However, pregnancy complications (P = 0.018) and a high likelihood of adverse pregnancy outcomes (P = 0.048) may still occur. Maternal gestational age (P &lt; 0.001), body mass index (P &lt; 0.001), library concentration (P &lt; 0.001), and fetal gender (P &lt; 0.001) were considered to be the associated factors for the initial low fetal fraction results. This may be associated with pregnancy complications (P &lt; 0.001) and a high likelihood of adverse pregnancy outcomes (P = 0.034). The body mass index (P = 0.015) and time between draws (P = 0.001) were associated with the second test’s success. The incidence of low fetal fraction samples was more frequent with blood collection tubes of the G type than with the K type (P &lt; 0.001). Conclusion Initial nonresults because of z-scores in the gray area did not imply an increased risk of aneuploidy, but vigilance is needed for an increased risk of pregnancy complications and adverse pregnancy outcomes. Because of the low fetal fraction, the initial absence of results may be related to the assay method, as well as the effect of blood collection tubes and the need to be alert to the risk of pregnancy complications and adverse pregnancy outcomes.

Exome sequencing for nonimmune hydrops fetalis and clinical utility of data reanalysis.

Nonimmune hydrops fetalis (NIHF) presents as life-threatening fluid collections in multiple fetal compartments and may be led by numerous etiologies. To establish the diagnostic yield of exome sequencing for single-gene disorders in unexplained NIHF and to evaluate the clinical utility of data reanalysis. A series of 53 unexplained cases of NIHF were enrolled, including 39 cases met a strict definition of NIHF, and 14 cases with increased nuchal translucency (NT) and/or cystic hygroma in combination with other fluid collections. Trio ES from fetal samples and parental blood was performed, and clinical reports were returned by geneticists and genetic counselors. Multidisciplinary team forums were conducted for accurate diagnoses and improved patient management. The clinical follow-up assessments were conducted, and the reanalysis was performed for cases with a non-positive result. Diagnostic variants were identified in 22.6% (12/53) of the cases, and variants of potential clinical significance were detected in an additional 13.2% (7/53) of the cases. Of them, 3 possible diagnoses (3/41, 7.3%) were obtained during reanalysis. Notably, half of the diagnosed cases were from the group exhibiting only skin edema and increased nuchal translucency and/or cystic hygroma. The diagnostic rate in this group was 42.8% (6/14), while in the classically defined NIHF group, the rate was 15.4% (6/39). The pregnancy termination and live birth rates of the cases with positive genetic testing results were found to be statistically significantly different from those with negative results (91.7% vs 53.6% and 8.3% vs 36.6%, P < 0.05 for both). ES provides high incremental diagnostic yield for NIHF after standard-of-care testing, and reevaluating non-diagnostic exomes in light of updated knowledge can maximize diagnostic yield. Identifying the etiology of NIHF facilitates prenatal diagnosis, improves the management of NIHF cases, and predicts recurrence risk in future pregnancies.

A rare cause of echogenic kidneys with oligohydramnios in the fetus: report of two different cases

BackgroundPrenatal ultrasound findings of fetal bilateral echogenic kidneys accompanied by oligohydramnios can be highly stressful for both pregnant women and physicians. The diversity of underlying causes makes it challenging to confirm a prenatal diagnosis, predict postnatal outcomes, and counsel regarding recurrence risks in future pregnancies.Case PresentationWe report two cases of abnormal fetal echogenic kidneys with oligohydramnios detected in the early third trimester. Autosomal recessive polycystic kidney disease (ARPKD), a rare genetic syndrome, was initially suspected in both cases. However, postnatal diagnoses differed: the first case was confirmed as glomerulocystic kidney disease (GCKD) through renal pathology, while the second case was diagnosed as ARPKD with a compound heterozygous likely pathogenic PKHD1 mutation.ConclusionPrenatal diagnosis of fetal echogenic kidneys with oligohydramnios should prioritize accurate diagnosis. Given the differences in the clinical spectrum, GCKD should be considered a differential diagnosis for this condition, particularly ARPKD. This study highlights the importance and benefits of molecular diagnosis and postnatal renal pathology for precise diagnosis and effective counseling.

Application of triplet-primer PCR technology for the genetic testing and prenatal diagnosis of patients with Myotonic dystrophy type 1

To explore the application of triplet-primer PCR (TP-PCR) for the genetic testing and prenatal diagnosis in patients with Myotonic dystrophy type 1 (DM1). A total of 60 individuals from 48 pedigrees undergoing genetic testing at the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from May 2018 to October 2022 were selected as the study subjects. TP-PCR combined with capillary electrophoresis was applied to determine the number of CTG repeats of the DMPK gene, and prenatal testing was provided to four DM1 pedigrees. This study was approved by the First Affiliated Hospital of Zhengzhou University (Ethics No. KS-2018-KY-36). A total of 52 DM1 patients were detected, mostly with muscle weakness, muscular atrophy and myotonia as the initial symptoms, along with typical myotonic potentials. Some patients also had abnormalities of other systems. The number of abnormal CTG repeats of the DMPK gene was > 50, whilst the number of CTG repeats on the normal allele had ranged from 5 to 18. The number of the most common normal CAG repeats was 6 (30.77%, 16/52). Among the four DM1 pedigrees undergoing prenatal diagnosis, one fetus was healthy, whilst three fetuses were found to have abnormal CTG repeats (> 50 times) and diagnosed with DM1. TP-PCR can diagnose DM1 patients with speed and accuracy. However, this method cannot accurately determine the number of CTG repeats when it exceeds 50.

Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with Complete androgen insensitivity syndrome due to a novel variant of AR gene

To explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS). A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome (SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070). The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46,XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c.1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister's first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PM4+PP3_Moderate+PP4). The c.1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians' thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction.

Genetic analysis of a child with autosomal recessive primary microcephaly due to variant of ASPM gene and a literature review

To explore the clinical and genetic characteristics of a child with autosomal recessive primary microcephaly (MCPH). A case study has been carried out on a boy who had presented at the Inner Mongolia Maternity and Child Health Care Hospital for microcephaly and mental deficiency in September 2022. Prenatal ultrasound images were retrospectively analyzed, and whole exome sequencing and Sanger sequencing were carried out for his family. A literature review was also carried out using keywords such as "ASPM gene", "microcephaly", "prenatal diagnosis", "primary microcephaly", "ASPM", "MCPH5", "MCPH", "autosomal recessive microcephaly", and "prenatal diagnosis on ultrasonography" on the PubMed database, Wanfang Data and China National Knowledge until September 2023. This study was approved by the Inner Mongolia Maternity and Child Health Care Hospital (Ethics No. 2021-093-1). The proband had shown progressive reduction in biparietal diameter (BPD) and head circumference (HC) during the fetal period. He was found to harbor compound heterozygous variants of the ASPM gene, which included a paternally derived c.8044C>T (p.R2682X) and a maternally derived c.8652dup (p.A2885Sfs*35). Both variants were classified as pathogenic (PVS1+PM2_Supporting+PP4; PVS1+PM2_Supporting+PM3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). For other fetuses in his family, prenatal ultrasound and genetic testing were all normal. Literature research has identified 11 relevant articles, which included 14 MCPH cases. All of the MCPH5 cases had shown various degrees of reduced BPD/HC on fetal imaging (100%, 15/15). Developmental delay, intellectual disability, and attention deficits were noted in all survived cases, with one case having seizures (12.5%, 1/8). Their genotypes had included homozygotes (46.2%, 6/13) and compound heterozygotes (53.8%, 7/13) for nonsense variants (45%, 9/20) and frameshifting variants (55%, 11/20). The compound heterozygous variants c.8044C>T (p.R2682X) and c.8652dup (p.A2885Sfs*35) of the ASPM gene probably underlay the reduced BPD and HC in this proband with MCPH.

Bovine aortic arch: a potential indicator that may not serve in prenatal diagnosis - a study based on fetal anatomy, genetics, and postnatal clinical outcomes

ObjectiveTo investigate the structural abnormalities, genetic results, and postnatal clinical outcomes of fetuses with bovine aortic arch (Bovine Aortic Arch, BAA) to provide a basis for prenatal counseling and management.MethodsA retrospective analysis was conducted on 216 fetuses diagnosed with bovine aortic arch through prenatal ultrasound screening at the First Affiliated Hospital of Anhui Medical University and the No.901 Hospital of the Joint Service of the People’s Liberation Army from January 2019 to February 2023. Their family history of genetic diseases, prenatal screening results, and postnatal follow-up data were collected. The fetuses were divided into an isolated BAA group (n = 192) and a non-isolated BAA group (n = 24). Chromosomal karyotyping and copy number variation (CNV) testing were conducted, and statistical analysis was performed using SPSS 22.0 software.ResultsOf the 216 fetuses with BAA, 192 were isolated BAA (88.89%), and 24 were non-isolated BAA (11.11%). Among the isolated BAA fetuses, only 1 case (0.52%) had chromosomal karyotype and pathogenic CNV abnormalities. Among the non-isolated BAA fetuses, 4 cases (16.67%) had chromosomal or CNV abnormalities, but the overall risk was low. The postnatal outcomes of isolated BAA fetuses were good (99.48%), while 79.17% of non-isolated BAA fetuses had good postnatal outcomes.ConclusionMost BAA fetuses are isolated, with a very low incidence of chromosomal abnormalities and pathogenic CNVs, and have good postnatal outcomes. The clinical value of isolated BAA is limited, and invasive prenatal diagnosis is not recommended for low-risk populations. Prenatal screening should focus on the risk of concurrent severe structural anomalies and chromosomal abnormalities.

Analysis of ACADVL gene variant in a Chinese pedigree affected with Very-long-chain acl-CoA dehydrogenase deficiency

To carry out genetic testing on a child diagnosed with Very-long-chain acyl-CoA dehydrogenase deficiency (VLADD) in order to provide a basis for genetic counseling and prenatal diagnosis for his family. Whole exome sequencing was performed for the proband. Candidate variant sites in the ACADVL gene were verified by Sanger sequencing, and their pathogenicity was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was performed on the fetus upon subsequent pregnancy. This study was approved by the Luoyang Maternal and Child Health Care Hospital (Ethics No. ). The proband was found to harbor compound heterozygous variants of the ACADVL gene, namely c.1532G>A and 1827+2_1827+12del, which were inherited from his mother and father, and classified as likely pathogenic and pathogenic, respectively. By combining the clinical manifestations of the proband and the results of blood tandem mass spectrometry and genetic testing, the child was ultimately diagnosed as cardiomyopathy type VLADD. Prenatal diagnosis showed that the fetus has carried the same compound heterozygous variants, and the couple had opted to terminate the pregnancy. The c.1532G>A/1827+2_1827+12del compound heterozygous variants of the ACADVL gene probably underlay the pathogenesis of VLADD in this pedigree. The discovery of the 1827+2_1827+12del variant has enriched the mutational spectrum of the ACADVL gene.

Prenatal diagnosis of a fetus with 15q11q13 complex duplication syndrome and a literature review

To explore the clinical features and genetic etiology of a fetus with 15q11q13 complex duplication syndrome. A fetus diagnosed with 15q11q13 duplication syndrome at Ningbo Women and Children's Hospital on April 19, 2023 was selected as the study subject. Clinical data was collected, and the fetus was subjected to invasive prenatal diagnosis including G-banded karyotyping and chromosomal microarray analysis (CMA). Following the discovery of chromosomal duplication, trio-whole exome sequencing was carried out to exclude single base variants and confirm the parental original of the duplication. Optical genome mapping was also performed to delineate the structural arrangement of the duplication. Relevant literature was searched in the PubMed, Wanfang Medical Network and CNKI databases using "15q11q13", "duplication", "hexasomy" and "Six fold repetition" as the key words from January 1, 2000 to August 1, 2023 for a review of previously reported 15q11q13 hexasomy cases. This study was approved by the Ningbo Women & Children's Hospital (Ethics No. EC2020-048). The fetus was found to have a mosaicism karyotype of 48,X?,+mar,+idic(15)(q13)[33]/47,X?,+idic(15)(q13)[17]. CMA and trio-WES have all shown a six-fold duplication in the PWS/AS critical region (PWACR) at 15q11.2q13.2 and quadruple duplication of 15q13.2q13.3 region, which have derived from its mother and formed supernumerary marker chromosomes (SMCs). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 15q11.2q13.2 sixfold duplication was classified as pathogenic, whilst the 15q13.2q13.3 quadruple duplication was classified as variant of uncertain significance. Literature search has identified 11 cases of 15q11q13 duplication involving hexasomy of the PWACR, with all cases showing mental retardation, language delay and hypotonia, and most of them also had motor retardation, epilepsy and mild facial dysmorphism. Hexasomy for the PWACR combined with tetrasomy of 15q13.2q13.3 probably underlay the left hand polydactyly, polyhydramnios and intrauterine growth retardation in this fetus.

Prenatal diagnosis and genetic analysis of two fetuses with Wolf-Hirschhorn syndrome

To explore the prenatal ultrasound phenotype and genetic basis of two fetuses with Wolf-Hirschhorn syndrome (WHS). A retrospective analysis was conducted on the ultrasound imaging data of two fetuses suspected for WHS at the Prenatal Diagnostic Center of Qingyuan People's Hospital in July 2017 and August 2019, respectively. Amniotic fluid samples of the two fetuses were subjected to chromosomal karyotyping and chromosomal microarray analysis (CMA). This study was approved by the Qingyuan People's Hospital (Ethics No. IRB-2022-064). Prenatal ultrasound examination of the two fetuses had consistently revealed WHS-associated traits including intrauterine growth restriction (IUGR), craniofacial abnormalities and cardiovascular anomalies. Karyotyping analysis suggested that both fetuses had harbored cryptic chromosomal translocations involving partial deletion of 4p. And parental verification revealed that it was de novo for fetus 1 and paternal for fetus 2. CMA has confirmed that fetus 1 had an approximately 8.7 Mb deletion at 4p16.3p16.1 and a 6.8 Mb duplication at 8p23.1p23.1, whilst fetus 2 had a 20.05 Mb deletion at 4p16.3p15.31 and a 7.66 Mb duplication at 9p24.3p24.1. The karyotype of fetus 1 was determined as 46,XN,der(4)t(4;8)(p16.1;p23.1)dn.arr[hg19]4p16.3p16.1(68345_8721580)×1, 8p23.3p23.1(158048_6933745)×3, and that of fetus 2 was determined as 46,XN,der(4)t(4;9)(p15.3;p24)pat.arr[hg19]4p16.3p15.31(68345_20116061)×1, 9p24.3p24.1(208454_7868292)×3. The 4p deletion is probably the main cause for the WHS phenotype in both fetuses. WHS should be suspected when IUGR, renal anomalies, craniofacial and cardiovascular abnormalities are detected upon prenatal ultrasound screening.