Case report and functional verification of a novel mutation in the interferon regulatory transcription factor 6 gene in a family with orofacial clefts.

BACKGROUND: This study aimed to identify the causative genetic variant in a Chinese family with orofacial clefts. METHODS: We retrospectively analyzed the clinical information of a family with orofacial clefts. Then, we performed an etiological genetic analysis of the family using whole exome sequencing analysis and Sanger sequencing. We created a hybrid code-shifting mutation cell line (293T-462het) and evaluated its impact on cell proliferation, migration, and apoptosis, as well as E-cadherin and vimentin expression. RESULTS: Whole exome sequencing revealed a novel heterozygous variant c.1386del (p.A462Pfs*28) in the interferon regulatory transcription factor 6 (IRF6) gene in a family with orofacial clefts. Sanger sequencing further confirmed that this heterozygous variant was the genetic cause of orofacial clefts in this family. The c.1386del variant of IRF6 was classified as likely pathogenic. The heterozygous mutation IRF6 (c.1386del) enhanced cell proliferation and migration while inhibiting cell apoptosis and regulating the expression of E-cadherin and vimentin. CONCLUSION: This study identified a novel c.1386del mutation in the IRF6 gene and explored how this mutation leads to lip and palate defects. Our results provide a solid theoretical foundation for future genetic detection of these orofacial defects.

Prenatal diagnosis and management of Apert syndrome in a low-middle income country: Case report.

INTRODUCTION AND IMPORTANCE: Apert syndrome is a rare autosomal dominant disorder characterized by craniosynostosis, midface hypoplasia, and syndactyly. Prenatal diagnosis of this condition can be challenging. This case report highlights the importance of recognizing characteristic ultrasound findings for timely diagnosis and genetic counselling. CASE PRESENTATION: A 37-year-old, gravida 1, para 0 woman underwent a routine third-trimester ultrasound at 31 weeks gestation. The examination revealed significant hydramnios, bilateral hand syndactyly, foot abnormalities, and an unusual head shape with a prominent forehead, flat occiput, hypertelorism, and low-set ears. These findings raised suspicion for Apert syndrome. Subsequent molecular analysis confirmed a mutation in the FGFR2 gene, confirming the diagnosis. Three-dimensional (3D) ultrasound imaging was utilized to provide the parents with a clearer understanding of the foetal anomalies, aiding in their decision-making process. Given the high risk of impaired intellectual development and the complexity of its management, the pregnancy was terminated at 33 weeks' gestation. CLINICAL DISCUSSION: This case emphasizes the role of comprehensive prenatal ultrasound in identifying potential foetal anomalies, even in the absence of prior risk factors. Characteristic sonographic findings, such as craniosynostosis, syndactyly, and hydramnios, should raise suspicion for the diagnosis, even in the absence of family history. Molecular confirmation through FGFR2 gene testing is essential for definitive diagnosis and informed genetic counselling. CONCLUSION: While Apert syndrome is rare, recognizing its characteristic sonographic features can facilitate timely diagnosis. The use of 3D ultrasound imaging can be invaluable in enhancing parental understanding and facilitating informed decision-making.

Successful intracytoplasmic sperm injection in a macrozoospermia case with novel compound heterozygous aurora kinase C (AURKC) mutations.

PURPOSE: To explore the application possibility of macrocephalic sperm from a patient with 100% macrocephalic sperm and AURKC gene variations. METHODS: We diagnosed a case of macrozoospermia with 100% macrocephalic sperm and 39.5% multi-tailed spermatozoa by morphological analysis. Whole-exome sequencing (WES) was used for the patient and his wife. Sanger sequencing technique was used to verify the AURKC mutations in the patient's parents and his offspring. Sperm's ploidy was tested by flow cytometry. The couple asked for intra-couple ART therapy. RESULTS: The patient presented novel compound heterozygous AURKC mutations (c.434C > T, c.497A > T) by WES. Sanger sequencing validation showed that variant of c.434C > T was observed in his father and c.497A > T was observed in his mother. Flow cytometry revealed that there existed a certain proportion of haploid sperm. Macrocephalic spermatozoa whose heads were smaller than the diameter of injection needle were selected for microinjection. A singleton pregnancy was achieved after embryo transfer. Prenatal diagnosis revealed that the fetus had normal chromosomal karyotype. Sanger sequencing technique showed that the fetus carried a c.434C > T mutation in one AURKC allele. A 3730 g healthy male fetus was delivered at term. CONCLUSION: Our study reported a successful live birth from a patient with definite AURKC gene variants and may provide insights for such patients to choose donor sperm or their own sperm.

Prenatal Diagnosis of Persistent Left Superior Vena Cava Using High-Definition Flow Render Mode and Spatiotemporal Image Correlation.

OBJECTIVE: This study aimed to assess the use of two-dimensional (2D) ultrasound combined with high-definition flow (HD-flow) render mode and spatiotemporal image correlation (STIC) in diagnosing and classifying fetal persistent left superior vena cava (PLSVC). METHODS: Overall, 114 cases of fetal PLSVC were diagnosed using 2D ultrasound combined with STIC, and 114 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to evaluate the effectiveness of the diagnostic approach. RESULTS: All 114 PLSVC cases were diagnosed using 2D ultrasound combined with STIC. Although the diagnostic coincidence rate of PLSVC in the HD-flow combined with STIC was similar to that in the 2D ultrasound combined with HD-flow (96.8 vs 96.2%), 2D ultrasound with STIC enabled dynamic visualization of the PLSVC, furthering prenatal diagnosis. These cases were classified as type I PLSVC: 80 cases of type Ia, 29 cases of type Ib, and 5 cases of type Ic. Seventy isolated PLSVC cases (61.4%) were noted, whereas 44 cases (35.6%) were associated with concomitant structural abnormalities. Intracardiac structural malformations accounted for the highest proportion (n = 53, 58.89%), followed by single umbilical artery and facial/bodily abnormalities (n = 10, 11.11%). CONCLUSION: Combining HD-flow and STIC complements 2D ultrasound in diagnosing and classifying fetal PLSVC, demonstrating significant clinical relevance.

Balancing key stakeholder priorities and ethical principles to design a trial comparing intervention or expectant management for early-onset selective fetal growth restriction in monochorionic twin pregnancy: FERN qualitative study.

OBJECTIVES: As part of the FERN feasibility study, this qualitative research aimed to explore parents' and clinicians' views on the acceptability, feasibility and design of a randomised controlled trial (RCT) of active intervention versus expectant management in monochorionic (MC) diamniotic twin pregnancies with early-onset (prior to 24 weeks) selective fetal growth restriction (sFGR). Interventions could include laser treatment or selective termination which could lead to the death or serious disability of one or both twins. DESIGN: Qualitative semi-structured interviews with parents and clinicians. Data were analysed using reflexive thematic analysis and considered against the Principles of Biomedical Ethics. PARTICIPANTS AND SETTING: We interviewed 19 UK parents experiencing (six mothers, two partners) or had recently experienced (eight mothers, three partners) early-onset sFGR in MC twin pregnancy and 14 specialist clinicians from the UK and Europe. RESULTS: Participants viewed the proposed RCT as 'ethically murky' because they believed that the management of sFGR in MC twin pregnancy should be individualised according to the type and severity of sFGR. Clinicians prioritised the gestational age, size, decrease in growth velocity, access to the placental vessels and acceptability of intervention for parents. Discussions and decision-making about selective termination appeared to cause long-term harm (maleficence). The most important outcome for parents and clinicians was 'live birth'. For clinicians, this was the live birth of at least one twin. For parents, this meant the live birth of both twins, even if this meant that their babies had neurodevelopmental impairment or disabilities. CONCLUSIONS: All three pregnancy management approaches for sFGR in MC twin pregnancy carry risks and benefits, and the ultimate goal for parents is to receive individualised care to achieve the best possible outcome for both twins. An RCT was not acceptable to parents or clinicians or seen as ethically appropriate. Alternative study designs should be considered to answer this important research question.

Prenatal Diagnosis, Course and Outcome of Patients with Truncus Arteriosus Communis.

Background: The objective of our study was to assess the prenatal course, associated anomalies and postnatal outcome and the predictive value of various prenatal parameters for survival in prenatally diagnosed cases of truncus arteriosus communis (TAC). Methods: We evaluated cases from four centers between 2008 and 2021. Results: In 37/47 cases (78.7%), classification into a Van Praagh sbtype was possible, most had TAC type A1 (18/37 = 48.6%). In 33/47 (70.2%) with available valve details on common trunk valve, most presented with tricuspid valves (13/33 = 39.4%). In the overall sample, 14/47 (29.8%) had relevant insufficiency, and 8/47 (17%) had stenosis. In total, 37/47 (78.7%) underwent karyotyping, with 15/37 (40.5%) showing abnormal results, mainly 22q11.2 microdeletion (9/37 = 24.3%). Overall, 17/47 (36.2%) had additional extracardiac anomalies (17/47 = 36.2%). Additional intracardiac anomalies were present in 30/47 (63.8%), or 32/47 (68.1%) if coronary anomalies were included. Four (8.5%) had major defects. Two (4.3%) intrauterine deaths occurred, in 10 (21.3%) cases, the parents opted for termination, predominantly in non-isolated cases (8/10 = 80.0%). A total of 35/47 (74.5%) were born alive at 39 (35-41) weeks. Three (8.6%) pre-surgical deaths occurred in non-isolated cases. In 32/35 (91.4%), correction surgery was performed. The postoperative survival rate was 84.4% (27/32) over a median follow-up of 51.5 months. Initial intervention was performed 16 (1-71) days postpartum, and 22/32 (68.8%) required re-intervention. Regarding prenatal outcome-predicting parameters, no significant differences were identified between the survivor and non-survivor groups. Conclusions: There exist limited outcome data for TAC. To our knowledge, this is the largest multicenter, prenatal cohort with an intention-to-treat survival rate of almost 85%.

Prenatal diagnosis of the umbilical cord torsion at the placental cord insertion site: A case report and literature review.

A 35-year-old woman (gravida 1, para 0) was admitted to our hospital at 28 weeks' gestation with vaginal bleeding from placenta previa. Severe fetal bradycardia was observed during fetal heart rate monitoring. Ultrasonography showed widely dilated veins on the fetal surface of the placenta and an extraordinarily low umbilical artery peak systolic velocity in the Doppler study. Umbilical cord torsion was suspected. On the subsequent day, we performed a cesarean section due to worsening fetal heart rate patterns. Umbilical artery blood gas analysis indicated severe acidemia (pH 7.063), and umbilical cord torsion was confirmed at the placental cord insertion site. Diagnosing UCT prenatally is challenging; however, it can be suspected by scanning for the widely dilated veins on the fetal placental surface, termed as the "Sunset Sign," an abnormally low umbilical artery peak systolic velocity, and other fetal Doppler abnormalities.

Prenatal diagnosis in estimating the prognosis of sacrococcygeal teratoma.

: Sacrococcygeal teratoma is a rare congenital malformation, the prognosis depends on factors affecting foetal development. The diagnosis is based on ultrasound examination, especially the evaluation of the detailed morphology of the foetus in the 20th week of pregnancy. Therefore, it is crucial to keep looking for ultrasound markers that would prenatally determine the most accurate prognosis for the foetus. Now, we rely on a small number of studies with a predominance of case reports. We offer a literature review of the essential information concerning sacrococcygeal teratoma diagnostics, therapy, and complications of sacrococcygeal teratomas in connection with prenatal diagnosis. It turns out that in cases with a favourable prognosis according to prenatal ultrasound examination and adequate surgical treatment after childbirth, the prognosis of this congenital malformation is excellent.

Prenatal diagnosis and family analysis of 17q12 microdeletion syndrome with fetal renal abnormalities.

Purpose: To analyze the prenatal diagnosis, parental verification, and pregnancy outcomes of three fetuses with 17ql2 microdeletion syndrome. Methods: We retrospectively reviewed 46 singleton pregnancies with anomalies in the urinary system who underwent amniocentesis from Feb 2022 to October 2023 in the Prenatal Diagnosis Center of Lianyungang Maternal and Child Health Hospital. These fetuses were subjected to chromosomal microarray analysis (CMA) and/or trio whole-exome sequencing (Trio-WES). We specifically evaluated these cases' prenatal renal ultrasound findings and clinical characteristics of the affected parents. Results: Three fetuses were diagnosed as 17q12 microdeletions, and the detection rate was 6.5% in fetuses with anomalies in the urinary system (3/46). The heterogeneous deletions range from 1.494 to 1.66 Mb encompassing the complete hepatocyte nuclear factor 1 homeobox B (HNF1B) gene. Fetuses with 17q12 deletion exhibited varied renal phenotypes. Moreover, the clinical phenotypes of the affected parents differed greatly in the two cases (case 2 and case 3) in which the deletion was inherited. For case 3, the mother manifested classic symptoms of 17q12 deletion syndrome as well as unreported characteristics, such as very high myopia. Conclusion: Our findings demonstrate the necessity and significance of offering prenatal genetic testing when various renal anomalies are detected. In addition, our study broadens the phenotypic spectrum of 17q12 deletions. Most importantly, our findings may allow timely supportive genetic counseling and guidance for pregnancy in affected families, e.g., with the help of preimplantation genetic testing (PGT).

Double Aortic Arch: A Comparison of Fetal CMR, Postnatal CT and Surgical Findings.

BACKGROUND: In double aortic arch (DAA) one of the arches can demonstrate atretic portions postnatally, leading to diagnostic uncertainty due to overlap with isolated right aortic arch (RAA) variants. The main objective of this study is to demonstrate the morphological evolution of different DAA phenotypes from prenatal to postnatal life using 3D fetal cardiac magnetic resonance imaging (CMR) and postnatal CT/CMR imaging. METHODS: 3D fetal CMR was undertaken in fetuses with suspected DAA over a six-year period (Jan 2016 - Jan 2022). All cases with surgical confirmation of DAA were retrospectively studied and morphology on fetal CMR was compared to postnatal CT/CMR and surgical findings. RESULTS: 32 fetuses with surgically confirmed DAA underwent fetal CMR. All demonstrated a complete DAA with left-sided arterial duct. The RAA was dominant in 30/32 (94%). Postnatal CT/CMR was undertaken at median age of 3.3months (IQR 2.0-3.9) demonstrating DAA with patency of both arches in 9/32 (28%), with 6 showing signs of coarctation of the left aortic arch (LAA). The LAA isthmus was not present on CT/CMR in 22/32(69%), the transverse arch between left carotid and left subclavian artery was not present in 1 case. CONCLUSIONS: Fetal CMR provides novel insights into perinatal evolution of DAA. The smaller LAA can develop coarctation or atresia related to postnatal constriction of the arterial duct, making diagnosis of DAA challenging with contrast-enhanced CT/CMR. This highlights the potentially important role for prenatal 3D vascular imaging and might improve intepretation of postnatal imaging.

Perinatal management for fetal oral epignathus with duplication of the pituitary gland (DPG)-plus syndrome: A case report and literature review.

The prenatal diagnosis of epignathus presents a unique challenge for physicians. Differential diagnosis is usually based on the anatomic location of the tumor. Typical prenatal ultrasound characteristics of epignathus include a mixed solid and cystic lesion with vascularity in the solid component, originating from the hard or soft palate, and it is often associated with other anomalies such as craniofacial clefts or trans-sphenoidal intracranial extension. Herein, we present a case of prenatal diagnosis of epignathus with rare ultrasonographic findings, prenatal management requiring collaborative efforts of a multidisciplinary team, and a well-planned innovative ex utero intrapartum treatment procedure. In addition, this report highlights the evolving postnatal diagnosis of the rare developmental anomaly, duplication of the pituitary gland-plus syndrome, which includes various midline craniofacial, central nervous system, spinal, and endocrine abnormalities.

Magnetic resonance imaging of fetal vascular malformations.

Vascular anomalies develop during fetal life and can be detected on prenatal ultrasonography and fetal magnetic resonance imaging. Diagnosis of lymphatic, venous, and arteriovenous malformations, as well as congenital hemangiomas and other congenital vascular tumors, may be challenging. The benign vascular anomalies may be difficult to differentiate from malignancies with a similar appearance. In this manuscript, we present a succinct overview of the congenital vascular anomalies that may present in fetal or neonatal life.

Mothers' reflections on the diagnosis and birth of their child with Down syndrome: Variability based on the timing of the diagnosis.

Previous research has examined parents' reflections on their child's Down syndrome diagnosis based on whether the diagnosis was provided prenatally or after birth, revealing few significant differences; by comparison, few studies have examined parents' reflections on the birth of the child in relation to the timing of the diagnosis. This study was conducted to examine whether mothers differentially reported on and rated the diagnosis, birth, and most recent birthday of their child with DS based on when the diagnosis was provided. Forty-four American mothers of children with DS discussed the birth of their child, when they learned of their child's DS diagnosis, and their child's most recent birthday with a researcher. Participants also completed online questionnaires on which they rated the events and indicated how they felt about the events at the time of their occurrence and at the time of the study. The results revealed that participants who received a prenatal diagnosis of DS for their child reflected differently-and seemingly more positively-on their child's birth relative to participants who received a postnatal diagnosis. These differences were evident when considering participant ratings, emotion language used when discussing the events, and feeling states characterizing how participants felt about the events at the time of their occurrence and at the time of the study. Given these group differences, medical professionals should carefully consider the conditions under which they provide mothers with diagnostic information and support services after a child is born.

Antenatal screening for fetal structural anomalies - Routine or targeted practice?

Antenatal screening with ultrasound identifies fetal structural anomalies in 3-6% of pregnancies. Identification of anomalies during pregnancy provides an opportunity for counselling, targeted imaging, genetic testing, fetal intervention and delivery planning. Ultrasound is the primary modality for imaging the fetus in pregnancy, but magnetic resonance imaging (MRI) is evolving as an adjunctive tool providing additional structural and functional information. Screening should start from the first trimester when more than 50% of severe defects can be detected. The mid-trimester ultrasound balances the benefits of increased fetal growth and development to improve detection rates, whilst still providing timely management options. A routine third trimester ultrasound may detect acquired anomalies or those missed earlier in pregnancy but may not be available in all settings. Targeted imaging by fetal medicine experts improves detection in high-risk pregnancies or when an anomaly has been detected, allowing accurate phenotyping, access to advanced genetic testing and expert counselling.

Prenatal diagnosis of ectopic kidney: Evaluation of characteristics, additional anomalies and urinary complications.

OBJECTIVE: To assess the characteristics, additional structural anomalies and postnatal urinary outcome of the cases diagnosed with fetal ectopic kidneys in the prenatal period. STUDY DESIGN: Cases having fetal ectopic kidneys, detected from a total of 14,617 pregnant women examined by routine detailed (Group 1) or indicated (Group 2) obstetric ultrasonography (USG) in a tertiary perinatology unit were analyzed. The prevalence of the cases, time of the diagnosis, sidedness of the affected kidney, anatomical location, origins of blood supply, additional urinary or extraurinary anomalies, and urinary complications during the postnatal follow-up period were investigated. RESULTS: We have detected 33 fetuses with ectopic kidneys in our cohort. The prevalence of fetal ectopic kidney was 0.22 %, with a median (min.-max.) diagnosis time of 21.3 (17.6-34) weeks. In the group in whom indicated USG was performed, the time of diagnosis was later compared to routine detailed USG (p = 0.04) group. There was no difference in terms of gender [male, (n = 14), female (n = 19), p = 0.38] and the sidedness of the ectopic kidneys (p = 0.38). The location of ectopic kidneys was most frequent in the iliac fossa (n = 20, 60.6 %) and in the lateral pelvic areas (n = 13, 39.3 %). The blood supply origin of ectopic kidneys was the common iliac artery in 22 (66.6 %), whereas the aorta in 11 cases (33.3 %). There was an additional urinary anomaly in 8 cases (24 %), an extraurinary structural anomaly, most commonly cardiac, and/or a soft marker for aneuploidy were presented in 16 cases (48 %). The most common urinary complication in the postpartum period was vesicoureteral reflux (n = 5). CONCLUSION: Ectopic kidney in the prenatal period is a rare structural anomaly that can equally affect both genders and both kidneys. Prenatal diagnosis is important for the diagnosis of additional anomalies and follow-up of postnatal complications.

Low-level mosaic trisomy 7 at amniocentesis in a pregnancy associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 7 cell line and a favorable fetal outcome.

OBJECTIVE: We present low-level mosaic trisomy at amniocentesis in a pregnancy associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 7 cell line and a favorable fetal outcome. CASE REPORT: A 40-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY in cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (7) × 2-3, (X,Y) × 1, consistent with 24% mosaicism for trisomy 7. Polymorphic DNA marker analysis on the DNA extracted from the uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 7. Prenatal ultrasound findings were normal. She was referred for genetic counseling at 19 weeks of gestation. No repeat amniocentesis was suggested, and continuing the pregnancy was advised. At 22 weeks of gestation, the result of soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) = 6.1 (normal < 38). She did not have preeclampsia. At 39 weeks of gestation, a 3346-g male baby was delivered without any phenotypic abnormality. aCGH analysis on the DNA extracted from cord blood and placenta revealed the result of arr (1-22) × 2, (X,Y) × 1 with no genomic imbalance in all tissues. When follow-up at age three months, the baby was normal in development and phenotype. The peripheral blood had a karyotype of 46,XY, and interphase fluorescence in situ hybridization (FISH) analysis using the bacterial artificial chromosome (BAC) probes of chromosome 7 showed disomy 7 cells in all 102/102 cells. CONCLUSION: Low-level mosaic trisomy 7 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 7 cell line and a favorable fetal outcome.

Prenatal diagnosis of familial 3p26.3p25.3 deletion in a pregnancy associated with a favorable fetal outcome and asymptomatic carrier parent and family members in three generations.

OBJECTIVE: We present prenatal diagnosis of familial 3p26.3p25.3 deletion in a pregnancy associated with a favorable fetal outcome and asymptomatic carrier parent and family members in three generations. CASE REPORT: A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age and the carrier of distal 3p deletion. She was phenotypically normal, and there was no family history of congenital anomalies. Amniocentesis revealed a karyotype of 46,XY,del(3)(p26.1). Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 46,XY,del(3)(p25.3). Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed the result of arr 3p26.3p25.3 (117,735-8,709,972) × 1.0 [GRCh37 (hg19)] with an 8.59-Mb deletion of 3p26.3p25.3 encompassing 14 OMIM genes of CHL1, CNTN6, CNTN4, IL5RA, TRNT1, CRBN, SETMAR, SUMF1, ITPR1, BHLHE40, ARL8B, GRM7, LMCD1 and SSUH2. Cytogenetic analysis of parental bloods revealed a karyotype of 46,XX,del (3) (p25.3) in the mother and 46,XY in the father. The woman's 69-year-old mother and her 2-year-old elder son carried the same aberrant chromosome of 3p25.3→p26.3 deletion by conventional cytogenetic analysis but manifested no phenotypic abnormality. aCGH analysis of the peripheral bloods showed that the woman's mother and her elder son had the same 8.59-Mb deletion of 3p26.3p25.3. The woman was advised to continue the pregnancy. At 39 weeks of gestation, a 3040-g healthy male baby was delivered. When follow-up at age 2½ years, the neonate was normal in development and showed no apparent phenotypic abnormality. CONCLUSION: Distal 3p deletion of 3p26.3p25.3 involving the OMIM genes from CHL1 to SSUH2 can be associated with no apparent phenotypic abnormality.

A systematic review of prenatally diagnosed vein of Galen malformations: prenatal predictive markers and management from fetal life to childhood.

Introduction: Vein of Galen malformations (VGMs) account for less than 1% of all intracranial vascular malformations. However, in fetal and pediatric populations, they represent the most common vascular malformation of the brain. For the effective management of this condition, an optimal knowledge of its prenatal and postnatal clinical features is mandatory. Methods: Articles published between 1 January 2003 and 31 January 2024, reported in PubMed and EMBASE, were evaluated for a systematic review analyzing the prenatal and postnatal features and management of fetal VGMs. Results: Thirty-one papers reporting information on 51 prenatally diagnosed VGMs were included. The most common prenatal features were fetal hydrocephalus (39%) and cardiomegaly (56%). Postnatal data for 43 VGM cases are described. The overall mortality was 58.14%. In total, 77.78% of the survivors had normal development. Conclusions: Close follow-up and a multidisciplinary approach are mandatory to manage this condition. Our study aimed to provide a guide for gynecologists, neonatologists, cardiologists, and neuroradiologists.

The effect of opting-in versus opting-out forming on the rate of reported variants of questionable significance in prenatal microarray.

OBJECTIVE: To examine the effect of patient-selected opt-in versus opt-out option on the rate of reported variants of uncertain clinical significance (VOUS) and high-frequency low-penetrant (HFLP) findings in prenatal microarray testing. METHODS: A standard microarray consent form in Israel includes a requirement to note patient choice to be or not to be informed about the presence of VOUS and HFLP variants. The original form was designed as an opting-out method, in which the women had to actively mark if they did not want to be informed about questionable findings. In the authors' Genetic Institute, the form was changed for an opting-in option in October 2019. In this study we have compared the rates of reported VOUS and HFLP variants between the opt-in and opt-out periods. RESULTS: Of the 1014 prenatal CMA tests, 590 (58.2%) were performed in the opt-out period. A significant decrease in the rate of women requesting to be informed of VOUS findings was noted (66.8% in opt-out period vs 34.0% in opt-in period), yielding a relative risk (RR) of 0.46 (95% confidence interval [CI] 0.39-0.53). Rate of women preferring to be informed of HFLP variants decreased from 75.3% to 48.1% (RR 0.52, 95% CI 0.45-0.60). DISCUSSION: We present a simple and effective method to decrease the rate of reported findings of questionable significance in the prenatal setting. These results are important not only for microarray results, but also for next-generation sequencing techniques, such as whole exome or genome sequencing.

Parent-reported genetic counselor adherence to the NSGC practice resource for communicating a potential prenatal diagnosis: Impact on the Down syndrome diagnosis experience.

In 2011, the National Society of Genetic Counselors (NSGC) published practice resources about communicating a prenatal or postnatal diagnosis of Down syndrome (DS). However, the impact of GC adherence to those recommendations on patient experiences has been unknown. The objective of this analysis was to investigate perceived GC adherence to professional recommendations for delivering a DS diagnosis and the impact on parental diagnosis experiences and the information and support offered. Parents of children with DS born between 2016 and 2021 completed a survey distributed by 12 local DS organizations and the national DS Diagnosis Network to assess prenatal diagnosis experiences and the provision of support and information by health professionals. Participants were queried about whether their GC followed specific recommendations from the NSGC practice resource. Respondents were also invited to describe their diagnosis experience. An overall perceived adherence score was calculated (percentage of elements GC demonstrated/total number of elements). Open-ended responses were inductively coded by a GC and GC student to identify categories and to perform a sentiment analysis where 1 was completely negative, 2 was mixed/more negative, 3 was neutral, 4 was mixed/more positive, and 5 was completely positive. The GCs were blinded to participants' perceived adherence scores while performing the sentiment analysis. Of the 242 parents who completed the survey, 161 respondents answered questions about GC's perceived practice resource adherence. The median perceived adherence score was 42.9% (IQR 21.4-71.4)%. A total of 61 people provided an open-ended response about their prenatal diagnosis experience with a GC and were assigned a sentiment score. The median sentiment score was 3 (IQR 1-5). Kendall's Tau analysis showed that higher perceived practice resource adherence was associated with more positive sentiment scores. These results suggest that NSGC practice resource adherence may improve the prenatal diagnosis experiences of parents of children with DS and have the potential to improve counseling outcomes.