Prenatal Diagnosis最新文献

{"title":"Correspondence on “Current Controversy in Prenatal Diagnosis: The Use of cfDNA to Screen for Monogenic Conditions in Low Risk Populations Is Ready for Clinical Use”","authors":"Julia Wynn, Jennifer Hoskovec","doi":"10.1002/pd.6655","DOIUrl":"https://doi.org/10.1002/pd.6655","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics and Outcomes of Intrauterine Blood Transfusion (IUT) for Infectious Etiologies","authors":"Jessian L. Munoz, Leticia Benitez, Cara Buskmiller, Ahmed A. Nassr, Michael A. Belfort, Magdalena Sanz Cortes, Roopali V. Donepudi","doi":"10.1002/pd.6671","DOIUrl":"https://doi.org/10.1002/pd.6671","url":null,"abstract":"ObjectiveCongenital viral infection may result in fetal anemia and thrombocytopenia. While intrauterine blood transfusions (IUTs) are more commonly performed for Rh alloimmunization, reports using IUT for infection have varying success. Our primary objective was to characterize the outcomes of patients undergoing IUT for infectious etiologies at our center compared with Rh disease.Study DesignThis was a case series of patients undergoing IUT from 2012–2023. Infectious etiologies were identified by maternal serologies and confirmed by amniotic fluid polymerase chain reactions (PCR). Clinical outcomes were obtained from electronic medical records.ResultsDuring the study period, 70 patients underwent IUT, 34% (24/70) for Rh alloimmunization and 17% (12/70) for infection. Those with infectious etiologies were more likely to be diagnosed at earlier gestational ages (22 vs. 25 weeks, <jats:italic>p</jats:italic> = 0.04), with hydrops (75 vs. 33%, <jats:italic>p</jats:italic> = 0.03), and thrombocytopenia (27 ± 33 × 10<jats:sup>3</jats:sup> vs. 163 ± 112 × 10<jats:sup>3</jats:sup>, <jats:italic>p</jats:italic> &lt; 0.01). Perinatal death was significantly greater in cases of CMV (4/5, 80%) compared to parvovirus (1/7, 14%) or Rh alloimmunization (5/24, 21%) (<jats:italic>p</jats:italic> = 0.02).ConclusionAnemias and thrombocytopenias related to fetal infection may be indications for IUT. Compared with Rh alloimmunization, IUT in fetal infections was performed significantly earlier, and hydrops were more common at the time of IUT. In the case of CMV, greater rates of IUFD (80%) were observed. Patients should be counseled on the various outcomes by indication.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Complications After Laser Surgery for Twin‐to‐Twin Transfusion Syndrome, a Cohort Study","authors":"M. Gijtenbeek, F. M. M. Prein, E. J. T. Verweij, J. M. Middeldorp, F. Slaghekke, M. C. Haak","doi":"10.1002/pd.6663","DOIUrl":"https://doi.org/10.1002/pd.6663","url":null,"abstract":"ObjectivesTo assess maternal complications after fetoscopic laser surgery (FLS) for the twin‐to‐twin transfusion syndrome (TTTS).MethodsAll consecutive cases treated with FLS for TTTS between 2008 and 2021 at the Leiden University Medical Center (LUMC) were included. We allocated complications in three timeframes: “Admission for laser surgery,” “pregnancy after laser,” and “delivery and third stage of labor.” Maternal complications were graded according to the Maternal and Fetal Adverse Event Terminology (MFAET) and for intra‐abdominal hemorrhage, the Common Terminology Criteria for Adverse Events (CTCAE).ResultsIn the study period, 637 mothers were treated for TTTS with FLS. There were 1559 occurrences of maternal complications. The rate of severe maternal complications (grade 3 or 4) was 8.0%. Severe complications consisted of six cases of severe intra‐abdominal hemorrhage, nine cases of severe hemorrhage in pregnancy, one with severe chorioamnionitis, 10 with severe preeclampsia/HELLP syndrome, and 25 with a severe postpartum hemorrhage.ConclusionsEven though it is the gold standard for treating TTTS, FLS comes at a risk to the mother which should not be neglected. And even though not all complications have serious consequences to the mother, the severe maternal complication rate of 8.0% should be added to the inherent risks for the fetus, and should be discussed with patients eligible for surgery in order to make an informed decision on treatment options.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNPscan Combined With CNVplex as a High‐Performance Diagnostic Method for Thalassemia","authors":"Xiaofeng Wei, Xingmin Wang, Fu Xiong, Xinhua Zhang, Dun Liu, Wanjun Zhou, Fei He, Xuan Shang","doi":"10.1002/pd.6661","DOIUrl":"https://doi.org/10.1002/pd.6661","url":null,"abstract":"ObjectiveThalassemia is a Mendelian‐inherited blood disorder with severe consequences, including disability and mortality, making it a significant public health concern. Therefore, there is an urgent need for precise diagnostic technologies. We introduce two innovative diagnostic techniques for thalassemia, SNPscan and CNVplex, designed to enhance molecular diagnostics of thalassemia.MethodsThe SNPscan and CNVplex assays utilize variations in PCR product length and fluorescence to identify multiple mutations. In the SNPscan method, we designed three probes per locus: two 5′ and one 3′, and incorporated allele identification link sequences into one of the 5′ probes to distinguish the alleles. The detection system was designed for 67 previously reported loci in the Chinese population for a specific genetic condition. CNVplex identifies deletion types by analyzing the specific positions of probes within the globin gene. This innovative approach enables the detection of six distinct deletional mutations, enhancing the precision of thalassemia diagnostics. We evaluated and refined the methodologies in a training cohort of 100 individuals with confirmed HBA and HBB genotypes. The validation cohort, consisting of 1647 thalassemia patients and 100 healthy controls, underwent a double‐blind study. Traditional diagnostic techniques served as the control methods.ResultsIn the training set of 100 samples, 10 mutations (Hb QS, Hb CS, Hb Westmead, CD17, CD26, CD41‐42, IVS‐II‐654, ‐‐<jats:sup>SEA</jats:sup>, −α<jats:sup>3.7</jats:sup> and −α<jats:sup>4.2</jats:sup>) were identified, consistent with those identified by traditional methods. The validation study showed that SNPscan/CNVplex offered superior molecular diagnostic capabilities for thalassemia, with 100% accuracy compared to 99.43% for traditional methods. Notably, the assay identified three previously undetected mutations in 10 cases, including two deletion mutations (Chinese <jats:sup>G</jats:sup>γ(<jats:sup>A</jats:sup>γδβ)<jats:sup>0</jats:sup> del and SEA‐HPFH), and one non‐deletion mutation (Hb Q‐Thailand).ConclusionsThe SNPscan/CNVplex assay is a cost‐effective and user‐friendly tool for diagnosing thalassemia, demonstrating high accuracy and reliability, and showing great potential as a primary diagnostic method in clinical practice.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging‐Based Prediction Parameters of Perinatal Morbidity and Mortality for Fetal Occipital Cephaloceles","authors":"Amber L. Gaulden, Usha D. Nagaraj, A. Scott Emmert, Shawn M. Vuong, Beth M. Kline‐Fath, Karin S. Bierbrauer, Smruti K. Patel","doi":"10.1002/pd.6660","DOIUrl":"https://doi.org/10.1002/pd.6660","url":null,"abstract":"ObjectiveFetal occipital cephaloceles display significant morphologic heterogeneity resulting in variable cognitive and survival outcomes. The purpose of this study was to determine if specific imaging findings could provide predictive information on the clinical outcomes of patients with occipital cephalocele.MethodsWe conducted a retrospective review of fetal occipital cephalocele patients. Fetal and post‐natal imaging studies were evaluated for multiple parameters including: cephalocele size, ellipsoid volume, herniation of various neural tissues, and microcephaly. Based on the presence of certain findings, an imaging score (range: 0–11) and cephalocele grade (range: 0–4) were calculated.ResultsHigher fetal and post‐natal imaging scores were positively correlated with higher cephalocele grade (<jats:italic>p</jats:italic> &lt; 0.0001). Higher cephalocele grade was positively correlated with cerebellum and occipital lobe involvement (<jats:italic>p</jats:italic> &lt; 0.05). A higher fetal cephalocele grade was associated with a significantly high risk of mortality (CI: 15.5–22.10; <jats:italic>p</jats:italic> &lt; 0.0001).ConclusionHigher imaging scores and cephalocele grade were associated with a greater risk of mortality and verbal and motor delays. Imaging factors that appear to play a role in increasing cephalocele grade include involvement of the cerebellum, occipital lobes, and microcephaly. These findings may help counsel parents regarding the post‐natal course of patients with occipital cephalocele.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potentially Missed Diagnoses in Prenatal Versus Postnatal Exome Sequencing in the Lack of Informative Phenotype: Lessons Learned From a Postnatal Cohort.","authors":"Dana Brabbing-Goldstein, Lily Bazak, Noa Ruhrman-Shahar, Gabriel Arie Lidzbarsky, Naama Orenstein, Marina Lifshiz-Kalis, Nurit Asia-Batzir, Yael Goldberg, Lina Basel-Salmon","doi":"10.1002/pd.6659","DOIUrl":"https://doi.org/10.1002/pd.6659","url":null,"abstract":"<p><strong>Objective: </strong>To investigate how many novel pathogenic (P) and likely pathogenic (LP) nonprotein-truncating or noncanonical splicing variants would be classified as variants of unknown significance (VUS) if they were detected in fetuses without abnormalities.</p><p><strong>Methods: </strong>The study included 156 patients with neurodevelopmental disorders diagnosed through postnatal exome sequencing. Causative P/LP nonprotein-truncating and noncanonical splicing variants were retrospectively reclassified in cases without specific prenatal manifestations, disregarding postnatal symptoms.</p><p><strong>Results: </strong>Of the 156 patients, 72 had a nontruncating or noncanonical splicing variant. Six patients were excluded for having more than one possible causative variant. Twelve patients had prenatal malformations known to be associated with the diagnosed disorder; therefore, variant interpretation remained unchanged. In 33 of the 54 remaining cases, the variant had been previously reported as P/LP. Reclassification of the other 21 LP/P variants revealed that 16 would have been classified as VUS if detected prenatally.</p><p><strong>Conclusion: </strong>In our cohort, ∼24% (16/66) of causative nonprotein-truncating/noncanonical splicing variants would have been classified as VUS if sequencing had been conducted during pregnancy. The potential for false-negative results, stemming from limitations in the phenotypic information available prenatally, should be discussed with prospective parents. The criteria for classifying and reporting variants in the prenatal setting may require adjustment.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Vascular Malperfusion and Anatomic Cord Abnormalities Are Prevalent in Pregnancies With Fetal Congenital Heart Disease.","authors":"Chrystalle Katte Carreon, Christina Ronai, Julia K Hoffmann, Wayne Tworetzky, Sarah U Morton, Louise E Wilkins-Haug","doi":"10.1002/pd.6650","DOIUrl":"https://doi.org/10.1002/pd.6650","url":null,"abstract":"<p><strong>Objective: </strong>Impairments in the maternal-fetal environment are associated with adverse postnatal outcomes among infants with congenital heart disease. Therefore, we sought to investigate placental anomalies as they related to various forms of fetal congenital heart disease (FCHD).</p><p><strong>Methods: </strong>We reviewed the placental pathology in singleton pregnancies with and without FCHD. FCHD was divided into separate categories (transposition physiology, obstructive left, obstructive right, biventricular without obstruction, and others). Exclusion criteria included other prenatally known structural malformations and/or aneuploidy. The significance threshold was set at p < 0.05 or False Discovery rate q < 0.05 when multiple tests were performed.</p><p><strong>Results: </strong>The cohort included 215 FCHD and 122 non-FCHD placentas. FCHD placentas showed increased rates of maternal vascular malperfusion (24% vs. 5%, q < 0.001) and cord anomalies (27% vs. 1%, q < 0.001). Placentas with fetal TGA demonstrated a lower rate of hypoplasia when compared with other FCHD types (1/39 vs. 51/176, Fisher's exact p = 0.015).</p><p><strong>Conclusion: </strong>Placental maternal vascular malperfusion is increased in FCHD. The prevalence of vascular malperfusion did not differ by FCHD type, indicating that CHD type does not predict the likelihood of placental vascular dysfunction. Further investigation of the placental-fetal heart axis in FCHD is warranted given the importance of placental health.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics and Outcomes of Fetal Cardiac Rhabdomyoma With or Without mTOR Inhibitors, a Systematic Review and Meta-Analysis.","authors":"Hiba J Mustafa, Ali Javinani, Makayla L Morning, Francesco D'Antonio, Giorgio Pagani, Poonam M Puranik, Asma Khalil, Alireza A Shamshirsaz","doi":"10.1002/pd.6640","DOIUrl":"https://doi.org/10.1002/pd.6640","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the characteristics and outcomes of fetal cardiac rhabdomyoma with or without prenatal use of mammalian target of rapamycin inhibitor (mTORi).</p><p><strong>Search strategy: </strong>We systematically searched PubMed, Scopus, and Web of Science until June 2023.</p><p><strong>Selection criteria: </strong>Studies reporting on pregnancies with fetal cardiac rhabdomyoma were included.</p><p><strong>Data collection and analysis: </strong>A meta-analysis of proportions was conducted only on studies that included three or more cases.</p><p><strong>Results: </strong>A systematic review included 61 studies reporting on 400 fetuses with cardiac rhabdomyoma, of which 52 studies (389 fetuses) had expectant management and 9 studies (11 fetuses) were managed with mTORi. The meta-analysis included 26 studies reporting on 354 fetuses. Prenatally, 14% (95% CI 4-36) had pericardial effusion, 13% (95% CI 6-27) had arrhythmia, 16% (95% CI 7-31) had outflow tract obstruction, and 10% (95% CI 4-21) had hydrops. Fetal demise occurred in 12% (95% CI 5-30). Before delivery, tumor size reduction was noted in 13%, and after birth in 58%. Following birth, 8% (95% CI 3-14) had neonatal death and 9% (95% 4-17) required cardiac surgery. 60% (95% CI 41-79) of cases were diagnosed with tuberous sclerosis. Seizures were reported only in cases with a tuberous sclerosis diagnosis (41/71 infants). For the 9 studies reporting all together on 11 fetuses with tuberous sclerosis receiving prenatal mTORi, they showed improvement in the size of cardiac rhabdomyoma as well as outflow obstruction and none had fetal demise or neonatal death, and none required postnatal cardiac surgery.</p><p><strong>Conclusions: </strong>We report on the natural history of prenatal cardiac rhabdomyoma, including characteristics, progression, and survival. We report 11 fetuses with tuberous sclerosis and cardiac rhabdomyoma receiving prenatal mTORi, showing promising results.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Resolution Haplotyping of the PAH Gene Enables Early Gestation Noninvasive Prenatal Diagnosis of Phenylketonuria and Evolution Analysis of Recurrent Pathogenic Variations.","authors":"Jingqi Zhu, Zhenhua Zhao, Shaojun Li, Yifan Zhou, Lingrong Kong, Xinyu Fu, Huanyun Li, Jun Feng, Weiqin Tang, Di Wu, Xiangdong Kong","doi":"10.1002/pd.6645","DOIUrl":"https://doi.org/10.1002/pd.6645","url":null,"abstract":"<p><strong>Background: </strong>The clinical performance of RHDO-based NIPD for PKU during early gestation remains under-evaluated. Furthermore, studies focused on SNP loci obtained by next-generation sequencing to analyze the genetic evolution of pathogenic variations in PKU is limited.</p><p><strong>Methods: </strong>Maternal peripheral blood, along with proband and paternal samples, was collected between 7 and 12 weeks of gestation. The PAH gene and surrounding high heterozygosity SNPs were targeted for enrichment and sequencing. Fetal genotypes were inferred using RHDO-based NIPD. High-resolution PAH haplotypes were used for the analysis of two common pathogenic variants in the Chinese population: c.728G>A and c.1238G>C.</p><p><strong>Results: </strong>Sixty one PKU families participated with an average fetal fraction of 6.08%. The median gestational age was 8⁺⁶ weeks. RHDO-based NIPD successfully identified fetal genotypes in 59 cases (96.72%, 59/62). Two cases failed because of insufficient informative SNPs. In addition, a recombination event was assessed in one fetus of 59 cases. Six, and three haplotypes were identified for c.728G>A(p.Arg243Gln) and c.1238G>C(p.Arg413Pro), respectively. Hap_3 and hap_8 were identified as the ancestral haplotypes for these pathogenic variants, with other haplotypes arising from mutations or recombination based on these ancestral haplotypes.</p><p><strong>Conclusions: </strong>This study validates the feasibility of an RHDO-based assay for NIPD of PKU in early pregnancy and introduces its application in the demonstration of founder effects in recurrent pathogenic variations, offering new insights into the evolutionary analysis of PAH variations.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal exome sequencing, a powerful tool for improving the description of prenatal features associated with genetic disorders.","authors":"Christel Thauvin-Robinet, Aurore Garde, Julian Delanne, Caroline Racine, Thierry Rousseau, Emmanuel Simon, Michel François, Sebastien Moutton, Odent Sylvie, Chloe Quelin, Godelieve Morel, Alice Goldenberg, Anne-Marie Guerrot, Gabriella Vera, Nicolas Gruchy, Cindy Colson, Odile Boute, Carine Abel, Audrey Putoux, Jeanne Amiel, Agnes Guichet, Bertrand Isidor, Caroline Deiller, Constance Wells, Caroline Rooryck, Marine Legendre, Christine Francannet, Rodolphe Dard, Sabine Sigaudy, Ange-Line Bruel, Hana Safraou, Anne-Sophie Denommé-Pichon, Sophie Nambot, Marie-Laure Humbert Asensio, Christine Binquet, Yannis Duffourd, Antonio Vitobello, Christophe Philippe, Laurence Faivre, Frédéric Tran-Mau-Them, Nicolas Bourgon","doi":"10.1002/pd.6623","DOIUrl":"https://doi.org/10.1002/pd.6623","url":null,"abstract":"<p><strong>Objective: </strong>Prenatal exome sequencing (pES) is now commonly used in clinical practice. It can be used to identifiy an additional diagnosis in around 30% of fetuses with structural defects and normal chromosomal microarray analysis (CMA). However, interpretation remains challenging due to the limited prenatal data for genetic disorders.</p><p><strong>Method: </strong>We conducted an ancillary study including fetuses with pathogenic/likely pathogenic variants identified by trio-pES from the \"AnDDI-Prenatome\" study. The prenatal phenotype of each patient was categorized as typical, uncommon, or unreported based on the comparison of the prenatal findings with documented findings in the literature and public phenotype-genotype databases (ClinVar, HGMD, OMIM, and Decipher).</p><p><strong>Results: </strong>Prenatal phenotypes were typical for 38/56 fetuses (67.9%). For the others, genotype-phenotype associations were challenging due to uncommon prenatal features (absence of recurrent hallmark, rare, or unreported). We report the first prenatal features associated with LINS1 and PGM1 variants. In addition, a double diagnosis was identified in three fetuses.</p><p><strong>Conclusion: </strong>Standardizing the description of prenatal features, implementing longitudinal prenatal follow-up, and large-scale collection of prenatal features are essential steps to improving pES data interpretation.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}