Prenatal Diagnosis最新文献

{"title":"Genetic Diagnosis and Clinical Features of Fetuses With Congenital Diaphragmatic Hernia.","authors":"Yan Lü, Yi Yu, Jiazhen Chang, Mengmeng Li, Xueting Yang, Xiya Zhou, Na Hao, Hua Meng, Zhenghong Li, Lishuang Ma, Hui You, Shan Jian, Ying Wang, Shengjie Li, Yiqing Yu, Kaili Yin, Mingming Wang, Yulin Jiang, Qingwei Qi","doi":"10.1002/pd.6727","DOIUrl":"https://doi.org/10.1002/pd.6727","url":null,"abstract":"<p><strong>Objective: </strong>Congenital diaphragmatic hernia (CDH) is a rare abnormality with highly heterogeneous genetic causes. This study investigated chromosomal and monogenic abnormalities in fetal CDH patients and evaluated the efficacy of chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) for genetic diagnosis. The clinical features of the patients were also evaluated.</p><p><strong>Methods: </strong>We evaluated the genetic and clinical data of 51 prenatally diagnosed fetuses with CDH. CMA was performed for every patient. If CMA did not yield diagnostic results, the samples were subjected to WES.</p><p><strong>Results: </strong>Compared with fetuses with isolated CDH (n = 42), those with non-isolated CDH (n = 9) presented a higher genetic diagnostic rate (22.2% vs. 2.4%). The overall diagnostic yield was 5.9%, comprising 3.9% from chromosomal microarray analysis (CMA) and an additional 2.0% from whole exome sequencing (WES). CMA identified (1) mosaic trisomy 18 in a patient with isolated CDH; and (2) 4q terminal deletion syndrome in a patient with non-isolated CDH. WES identified a novel missense mutation, PLS3 c.1763A > G, associated with X-linked CDH in a patient with non-isolated CDH and a family history of recurrent CDH.</p><p><strong>Conclusion: </strong>Genetic testing should be offered for all fetuses with CDH, regardless of whether the cases are isolated or non-isolated. WES should be considered if CMA fails to provide a diagnostic result, particularly in patients with non-isolated CDH and a family history of recurrent CDH.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838765","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":"Going Back in Time: Prenatal Presentations of Postnatal Genetic Diagnoses Made in a Neonatal Intensive Care Unit.","authors":"Michael Duyzend, Malika Sud, Alissa M D'Gama, Tabitha Poorvu, Judy Estroff, Monica H Wojcik","doi":"10.1002/pd.6710","DOIUrl":"https://doi.org/10.1002/pd.6710","url":null,"abstract":"<p><strong>Objectives: </strong>Prenatal genetic diagnosis can impact care across the perinatal continuum; however, prenatal suspicion for genetic disorders may be complicated by incomplete knowledge of fetal rare-disease phenotypes. Here, we describe the prenatal presentations of a cohort of infants with rare genetic conditions who were diagnosed postnatally in a neonatal intensive care unit (NICU), to characterize prenatal presenting features and evaluate why the diagnosis was not identified prenatally.</p><p><strong>Methods: </strong>Retrospective cohort study of infants born over a 7 year period (2017-2023) who were admitted to a Level IV NICU and received a postnatal genetic diagnosis prior to 1 year of age. We identified which of these infants had been imaged prenatally at our Maternal Fetal Care Center (MFCC) as an opportunity for prenatal genetic diagnosis. Clinical data were abstracted from the medical records.</p><p><strong>Results: </strong>51 cases met the inclusion criteria. Nine of the 51 infants were not strongly suspected to have a genetic syndrome prenatally when seen at the MFCC, as evidenced by lack of prenatal genetic consultation and lack of documented suspicion for a genetic etiology. These cases largely had absent or uncertain prenatal phenotypes. In most cases (42/51, 82.4%), prenatal diagnostic testing was not pursued even if offered. Overall, postnatal diagnoses, of which there was one dual diagnosis, were made by karyotype/FISH (11/52, 21.1%), microarray (8/52, 15.4%), gene panel/targeted testing (17/52, 32.7%), or exome sequencing (16/52, 30.8%).</p><p><strong>Conclusions: </strong>Our data illustrate the challenges in fetal phenotyping and support a broad approach to prenatal testing to facilitate early genetic diagnosis, which may meaningfully impact postnatal care.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786776","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":"Identification of a Mosaic Variant in the SYNCRIP Gene Causing Foetal Periventricular Nodular Heterotopia, Abnormal Sulcation and Infratentorial Anomaly.","authors":"Roee Birnbaum, Gustavo Malinger, Liat Ben Sira, Mirela Goldenberg-Furmanov, Hadas Miremberg, Mordechai Shohat, Karina Krajden Haratz","doi":"10.1002/pd.6698","DOIUrl":"10.1002/pd.6698","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1659-1662"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting the Difficult Neonatal Airway in Fetuses With Micrognathia, Oropharyngeal or Neck Mass Lesions: Two-Center Experience With Fetal MRI.","authors":"Stacy Goergen, James Christie, Tracy Jackson, Maria-Elisabeth Smet, Simon Robertson, Atul Malhotra, Annie Kroushev, Mark Lovell","doi":"10.1002/pd.6651","DOIUrl":"10.1002/pd.6651","url":null,"abstract":"<p><strong>Objective: </strong>Neonatal airway compromise requiring intubation, due to micrognathia or a mass lesion obstructing the fetal airway, remains difficult but important to predict prenatally. We aimed to validate MR predictors of difficult neonatal airway (DNA) in a multicentre retrospective cohort of fetuses with micrognathia and oropharyngeal/neck masses.</p><p><strong>Method: </strong>The radiology databases of two large Australian maternal-fetal medicine centers were searched for subjects meeting inclusion criteria: Pregnancies of > 18 weeks' gestation evaluated with prenatal ultrasound and MRI between 2007 and 2022 where either fetal micrognathia or a fetal cervical, oral or oropharyngeal mass was identified on prenatal ultrasound and MRI, and details of delivery/postnatal course were available including: nature of delivery, need for the fetal airway to be secured at delivery, degree of difficulty in airway securement, survival > 24 h postnatally. Imaging predictors of a difficult neonatal airway (DNA) were assessed blinded to these neonatal outcomes.</p><p><strong>Results: </strong>Twenty-six fetuses met the inclusion criteria. Oropharyngeal and neck mass location with polyhydramnios was 100% sensitive and 82% specific for DNA. JI < 5th centile with polyhydramnios was 83% sensitive and 70% specific. JI < 5th centile with polyhydramnios was associated with DNA in 80% of cases delivered by ex utero intrapartum (EXIT) delivery and none with non-EXIT delivery mode.</p><p><strong>Conclusion: </strong>A cervical or oropharyngeal mass with polyhydramnios predicted a difficult neonatal airway. Polyhydramnios with jaw index < 5th centile was less sensitive and less specific for a difficult neonatal airway.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1593-1602"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypospadias Associated With Fetal Growth Restriction: A Multicentric Descriptive and Prognostic Cohort Study.","authors":"Manon Marquet, Olivia Anselem, Claire Bouvattier, Alexandre J Vivanti, Alexandra Benachi, Jean-Marie Jouannic, Olivier Picone, Jonathan Rosenblatt, Laurent J Salomon, Vassilis Tsatsaris, Yoann Athiel","doi":"10.1002/pd.6699","DOIUrl":"10.1002/pd.6699","url":null,"abstract":"<p><strong>Objective: </strong>To determine the prevalence of genetic and endocrine abnormalities and to assess fetal, neonatal and surgical outcomes in cases of hypospadias associated with fetal growth restriction.</p><p><strong>Method: </strong>A multicentric retrospective study was conducted across five prenatal diagnosis centers in Paris. The cohort encompassed all fetuses diagnosed with the combination of fetal growth restriction < 10th percentile (FGR) and hypospadias from 2013 to 2021. Maternal data, fetal outcome and results of prenatal investigations were collected, along with postnatal data, encompassing endocrinological and genetic assessments, functional aspects and surgical outcomes.</p><p><strong>Results: </strong>Among the 82 patients included in the cohort, there were 14 (17%) terminations of pregnancy and four (5%) in utero deaths, leaving 64 (78%) live neonates, including five (6%) with early neonatal death. Among the 52 (63%) cases where hypospadias and FGR were considered as ultrasound-isolated anomalies, six (12%, [3.2%-20.8%]) exhibited chromosomic, genetic, or endocrinological abnormalities diagnosed half prenatally and half postnatally. Fifty percent of the overall hypospadias were proximal. Most children underwent surgical intervention before reaching 2 years of age, with 50% encountering complications and often required reintervention.</p><p><strong>Conclusion: </strong>The association of FGR and hypospadias should not be underestimated as genetic or endocrinological abnormalities were identified even when hypospadias and FGR initially appear isolated. Additionally, the overall prognosis may be worsened using complex and iterative surgical procedures.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1567-1573"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parental Management Choices and Discordant Ultrasound Findings in Referrals for Fetal Spina Bifida.","authors":"Emma Van den Eede, Simen Vergote, Lennart Van der Veeken, Francesca Russo, Johannes Van der Merwe, Sofia Mastrodima-Polychroniou, Luc De Catte, Jan Deprest","doi":"10.1002/pd.6677","DOIUrl":"10.1002/pd.6677","url":null,"abstract":"<p><strong>Objective: </strong>The severity of spina bifida aperta can be assessed prenatally by ultrasound. Morphological findings assist parents in choosing between management options. We aimed to document those management choices since the introduction of fetal surgery, and compare initial ultrasound findings prior to referral to findings in a fetal surgery center.</p><p><strong>Method: </strong>Single center cohort study of 245 consecutive fetuses with a second-trimester diagnosis of SBA. Data included nature of referral (for assessment or for surgery), condition-specific findings on ultrasound, and further management. We compared the reported findings on the initial ultrasound to ours for the presence of hindbrain herniation, lesion level, ventricular width, kyphosis, leg movement, and club feet.</p><p><strong>Results: </strong>Seventy-two percent (n = 177) of fetuses met the eligibility criteria for surgery; in 60% (n = 106) parents opted for fetal surgery. Of 136 patients specifically referred for surgery, 27 were ineligible (20%). Of the others, 93 proceeded with surgery. In up to 28% (n = 30) of surgery referrals, eligibility criteria such as lesion level (n = 30, 28%) or leg movement (72%, n = 78) as severity indicators were not reported.</p><p><strong>Conclusion: </strong>Fetal surgery uptake was high in patients referred for surgery. Second assessment in a fetal surgery center often reveals additional relevant information.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1628-1634"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392673","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":"Agenesis of the Ductus Venosus and Its Association With Genetic Abnormalities.","authors":"Yarin Mash, Ron Bardin, Yinon Gilboa, Yossi Geron, Asaf Romano, Eran Hadar, Dana Brabbing Goldstein, Bella Davidov, Ohad Houri","doi":"10.1002/pd.6678","DOIUrl":"10.1002/pd.6678","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the association of agenesis of the ductus venosus (ADV) with genetic abnormalities using genetic studies-Chromosomal Microarray Analysis (CMA) and Exome Sequencing (ES).</p><p><strong>Design: </strong>Retrospective study of all fetuses diagnosed with ADV between January 2013 and December 2022 in a tertiary center.</p><p><strong>Results: </strong>ADV was diagnosed in 33 fetuses. The diagnosis was made at a mean gestational age of 21.2 ± 8.4 weeks. Conventional karyotype was applied in a single fetus (3.0%), CMA was applied in 21 fetuses (66.7%), and five fetuses (22.8%) were additionally tested with ES. ADV was isolated in eight fetuses (24%), whereas in 25 (76%) it was associated with abnormal ultrasound findings, including increased nuchal translucency (NT), intrauterine growth restriction (IUGR) and variable structural malformations, mostly cardiac (42%) followed by central nervous system (CNS) and skeletal malformations (24%). Genetic abnormalities were found in six fetuses out of 22 investigated (27%), of which 3 were detected by ES, 3 by CMA and 1 by conventional karyotype. A higher incidence of genetic aberrations was evident among ADVs associated with abnormal ultrasound findings. Genetic abnormalities were indicative of Prader Willi/Angelman syndrome, Noonan syndrome, CASK related disorder, 16q24.3 microdeletion syndrome and Trisomy 21.</p><p><strong>Conclusion: </strong>ADV associated with abnormal ultrasound findings is commonly correlated with genetic abnormalities and consequently unfavorable pregnancy outcomes. Our study emphasizes the value of genetic studies chiefly among cases associated with abnormal ultrasound findings, enabling early diagnosis of fetal pathologies associated with ADV, and providing better parental counseling.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1585-1592"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do We Really Want to Go Fishing for Foetal CC Dysgenesis (Whatever This Means…)? Extreme Caution is Needed.","authors":"Dario Paladini","doi":"10.1002/pd.6704","DOIUrl":"10.1002/pd.6704","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1675-1676"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626437","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 Ultrasonographic Features Associated With ARSL and X-Linked Chondrodysplasia Punctata 1 (CDPX1): Literature Review and Case Series.","authors":"Eleanor Broeren, Samantha Stover, Katya Bennett, Jessica Giordano, Stephanie Galloway, Julie Lauzon, Laura Rust, Manon Suerink, Arie van Haeringen, Rebecca Reimers","doi":"10.1002/pd.6649","DOIUrl":"10.1002/pd.6649","url":null,"abstract":"<p><strong>Background: </strong>Chondrodysplasia punctata 1 (CDPX1) is an X-linked recessive disorder of cartilage and bone development characterized by stippling on the cartilage and bone, flattened nasal bridge, and brachydactyly, or short fingers. CDPX1 has been associated with variants in the ARSL gene and is known to manifest prenatally, however, there has been no systematic literature review on this evidence.</p><p><strong>Aims: </strong>Here, we reviewed the current literature on prenatal manifestations of CDPX1, and additionally introduce previously unpublished cases.</p><p><strong>Materials & methods: </strong>A systematic review of the literature was performed. Additionally, a GeneMatcher submission was created and a call for cases was presented at the Fetal Sequencing Consortium meetings to find previously unpublished cases.</p><p><strong>Results: </strong>For the 22 fetuses reported here, we found that 55% had nasal hypoplasia, 41% had bony stippling or calcifications, 32% had polyhydramnios, 5% had oligohydramnios, 23% had shortened long bones, 23% had spinal canal stenosis, 18% had ventriculomegaly, 9% had brachydactyly/brachytelephalangy, 9% had clubbed feet, 9% had premature rupture of membranes, and 9% had intraventricular hemorrhage detected through sonography or radiography. We also found 17 unique variants in ARSL for these 22 fetuses.</p><p><strong>Discussion: </strong>A previously unpublished association of ARSL variants with intrauterine fetal death or stillbirth has been noted in this study. It is also possible that intracranial hemorrhage is an underrecognized feature associated with CDPX1 variation. However, there have been challenges in applying ACMG criteria to ARSL, a gene without an associated Variant Curation Expert Panel.</p><p><strong>Conclusion: </strong>This literature review and case series highlights which features of CDPX1 manifest prenatally, as well as introduces new phenotypes that have not been previously identified.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1663-1670"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308377","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":"Aberrant Fetal Brain Sulcus Formation: A Clue to the Diagnosis of Sotos Syndrome.","authors":"Caiqun Luo, Yang Liu, Hui Wang, LiYuan Chen, XiaoXia Wu, Qian Geng, Huaxuan Wen, Shengli Li, Weiqing Wu, Mei Zhong","doi":"10.1002/pd.6686","DOIUrl":"10.1002/pd.6686","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to elucidate two distinct fetal ultrasound features associated with aberrant brain sulcus formation as potential prenatal markers for Sotos syndrome caused by mutations in the NSD1 gene.</p><p><strong>Method: </strong>This retrospective study investigated three fetuses across two pregnancies, including a pair of monochorionic diamniotic twins, all diagnosed with Sotos syndrome via whole exome sequencing (WES). Comprehensive clinical and laboratory data were collected and analyzed. Each fetus underwent a series of specialized neurosonographic assessments to evaluate the development of the cerebral cortex.</p><p><strong>Results: </strong>All three fetuses exhibited aberrant brain sulcus formation characterized by Sylvian fissure (SF) abnormalities and shallow parietooccipital sulcus (POS). WES revealed the presence of two de novo NSD1 variants in these fetuses.</p><p><strong>Conclusions: </strong>Fetal aberrant brain sulcus formation may represent a distinctive ultrasound feature indicative of Sotos syndrome, thereby offering additional diagnostic insights for the identification of this condition.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1641-1646"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}