Prenatal Diagnosis最新文献

{"title":"Prenatal exome sequencing for the morphologically normal fetus: Should we be doing it?","authors":"Zhi Gao, Xiaofan Zhu, Huanan Ren, Yanfei Wang, Chunxiao Hua, Xiangdong Kong","doi":"10.1002/pd.6624","DOIUrl":"10.1002/pd.6624","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to investigate the yield of prenatal exome sequencing (pES) in morphologically normal fetuses.</p><p><strong>Method: </strong>This retrospective study analyzed 254 families with morphologically normal fetuses who underwent prenatal trio exome sequencing based on parental request between September 2020 and October 2023.</p><p><strong>Results: </strong>Overall, abnormal findings were detected in 8 families (3.1%, 8/254) by pES. Among these, 6 families (2.3%, 6/254) were found to have fetuses affected with monogenic disorders (2 autosomal recessive conditions and 4 autosomal dominant conditions), while 2 families (0.8%, 2/254) were incidentally found to be couples at risk of having a future pregnancy with a recessive condition. Among the six fetuses detected with monogenic disorders, two fetuses carried a de novo variant in OPA1 and NF1, which are known to cause Optic atrophy 1 and Neurofibromatosis, respectively. One fetus was detected with a maternally inherited variant in PKD2 related to polycystic kidney disease 2 (not known to the mother until then). One fetus was detected with a maternally inherited variant in SDHB associated with Pheochromocytoma. Two fetuses carried compound heterozygous variants in NAGLU and GJB2 associated with Mucopolysaccharidosis type IIIB and Deafness, respectively. In the 2 families where parents were found to be carriers but the fetuses were unaffected, heterozygous variants in the GJB2 and SERPINB7 genes were detected in the parents, respectively, which are associated with deafness and palmoplantar keratoderma.</p><p><strong>Conclusion: </strong>Our research indicated that pES can provide significant critical information for families with morphologically normal fetuses. Prenatal screening with exome sequencing requires careful management and detailed pre-test and post-test genetic counseling.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"287-293"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306685","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":"Exome sequencing in every pregnancy? Results of trio exome sequencing in structurally normal fetuses.","authors":"Michal Levy, Shira Lifshitz, Mirela Goldenberg-Fumanov, Lily Bazak, Rayna Joy Goldstein, Uri Hamiel, Rachel Berger, Shlomo Lipitz, Idit Maya, Mordechai Shohat","doi":"10.1002/pd.6585","DOIUrl":"10.1002/pd.6585","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to assess the detection rate of clinically significant results of prenatal exome sequencing (pES) in low-risk pregnancies and apparently normal fetuses in non-consanguineous couples.</p><p><strong>Methods: </strong>A retrospective analysis of pES conducted at a single center from January 2020 to September 2023 was performed. Genetic counseling was provided, and detailed medical histories were obtained. High-risk pregnancies were excluded due to major ultrasound anomalies, sonographic soft markers, abnormal maternal biochemical screening, or family history suggestive of monogenic diseases as well as cases with pathogenic and likely pathogenic (P/LP) chromosomal microarray results. Exome analysis focused on ∼2100 genes associated with Mendelian genetic disorders. Variant analysis and classification followed the American College of Medical Genetics and Genomics (ACMG) guidelines.</p><p><strong>Results: </strong>Among 1825 pES conducted, 1020 low-risk cases revealed 28 fetuses (2.7%) with potentially clinically significant variants indicating known monogenic diseases, primarily de novo dominant variants (64%). Among these 28 cases, 9 fetuses (0.9%) had the potential for severe phenotypes, including shortened lifespan and intellectual disability, and another 12 had the potential for milder phenotypes. Seven cases were reported with variants of uncertain significance (VUS) that, according to the ACMG criteria, leaned toward LP, constituting 0.7% of the entire cohort. Termination of pregnancy was elected in 13 out of 1020 cases (1.2%) in the cohort, including 7/9 in the severe phenotypes group, 2/12 in the milder phenotype group, and 4/7 in the VUS group.</p><p><strong>Conclusion: </strong>The 2.7% detection rate highlights the significant contribution of pES in low-risk pregnancies. However, it necessitates rigorous analysis, and comprehensive genetic counseling before and after testing.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"276-286"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912467","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":"Use of Prenatal Exome Sequencing: Opinion Statement of the French Federation of Human Genetics Working Group.","authors":"Guillaume Cogan, Marie-Bérengère Troadec, Françoise Devillard, Marie-Hélène Saint-Frison, David Geneviève, François Vialard, Emmanuelle Rial-Sebbag, Delphine Héron, Tania Attie-Bitach, Alexandra Benachi, Pascale Saugier-Veber","doi":"10.1002/pd.6692","DOIUrl":"10.1002/pd.6692","url":null,"abstract":"<p><strong>Objective: </strong>Prenatal whole exome sequencing (pES) is increasingly prescribed for fetuses with ultrasound anomalies. Starting from the local French prenatal medicine practice, healthcare system and legal landscape, we aimed to address the broad medical and ethical issues raised by the use of pES for women and couples as well as for prenatal care providers.</p><p><strong>Method: </strong>The French Federation of Human Genetics established a working group composed of clinicians and biologists from all over France to discuss pES challenges. A literature review was also performed.</p><p><strong>Results: </strong>We emphasize the importance of non-directive information that helps couples make a decision that is consistent with their personal values and ideas. We address the difficulty of obtaining informed consent that respects the couple's autonomy, despite the complexity of the information and regardless of their level of education and cultural background. We address whether variants of uncertain significance and unsolicited results should be reported. We emphasize the need for national harmonization of access to pES and the need for multidisciplinary meetings in complex situations. We point out that the specific French context of healthcare financing and the French law have a major influence on medical care organization and support for couples. The outcome of the working group is the development of 12 proposals.</p><p><strong>Conclusion: </strong>This opinion statement, dedicated to prenatal care providers worldwide although linked to the French context, will provide food for thought and assist them in understanding the complexity and implications of pES.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"299-309"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626490","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":"Prenatal Diagnosis of KBG Syndrome: Phenotypic and Genotypic Features of 12 Fetal Cases With the Disorder.","authors":"Xiang-Yi Jing, Qiu-Xia Yu, Li Zhen, Zhi-Qing Xiao, Dong-Zhi Li","doi":"10.1002/pd.6768","DOIUrl":"https://doi.org/10.1002/pd.6768","url":null,"abstract":"<p><strong>Objective: </strong>To present prenatal sonographic features, genomic results, and pregnancy outcomes of fetuses with KBG syndrome (KBGS).</p><p><strong>Method: </strong>This was a retrospective study of 12 cases with KBGS diagnosed by prenatal ultrasound and confirmed by genetic testing. Clinical and laboratory data were collected for these cases, including maternal demographics, prenatal sonographic findings, molecular test results, and pregnancy outcomes.</p><p><strong>Results: </strong>Twelve cases of KBGS were diagnosed prenatally with confirmatory genetic testing. Five had an abnormal first-trimester ultrasound with increased nuchal translucency (NT). Seven cases had a normal first-trimester ultrasound. Among these, four had mild ventriculomegaly in the second or third trimester, one had an arachnoid cyst found at 22 weeks, one had umbilical-systemic shunt, ventriculomegaly and polyhydramnios found at 24 weeks, and one presented with fetal growth restriction at 30 weeks. Four pregnancies continued to term, and infants presented with the classic phenotype of KBGS at a follow-up of 12 months. All ANKRD11 alterations in the 12 cases were de novo, and were characterized as either deletions encompassing ANKRD11 or loss-of-function variants.</p><p><strong>Conclusion: </strong>Increased NT and mild ventriculomegaly are two common sonographic features of fetal KBGS. Prenatal diagnosis of KBGS can be achieved with ultrasound and comprehensive molecular testing.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516255","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 Diagnosis of Shwachman-Diamond Syndrome: Fetal Compound Heterozygous Variants in the SBDS Gene Associated With Mildly Straight Ribs.","authors":"Linyan Zhu, Xuhong Wang, Yubo Shi, Xiaxi Huang, Huiqing Ding","doi":"10.1002/pd.6762","DOIUrl":"https://doi.org/10.1002/pd.6762","url":null,"abstract":"<p><p>Shwachman-Diamond Syndrome (SDS) is a rare genetic disorder with pancreatic insufficiency, bone marrow failure, and skeletal abnormalities. Prenatal diagnosis is rare, with only one previous case. We report a novel antenatal SDS diagnosis at 22 weeks gestation. Ultrasound showed mildly straightened fetal ribs without significant shortening. Whole exome sequencing identified pathogenic variants in the SBDS gene, confirming SDS. This highlights the importance of subtle rib anomalies in prenatal ultrasound for SDS detection. It expands the prenatal phenotypic spectrum and emphasizes the need for further research. Genetic diagnosis is crucial for counseling, pregnancy management, and recurrence risk assessment.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516334","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":"A Qualitative Study of Pregnant Patient Perspectives on Genetic Privacy of Cell-Free DNA and Optimal Design of a Prenatal Genetics Video-Based Educational Intervention.","authors":"Margaret M Thorsen, Rose C Mahoney, Christian Parobek, Paola C Jiménez Muñoz, Stephanie Nunez, Adam K Lewkowitz, Carolyn Slack, Melissa L Russo","doi":"10.1002/pd.6769","DOIUrl":"10.1002/pd.6769","url":null,"abstract":"<p><strong>Objective: </strong>To receive feedback on the design and content of a prenatal genetics video tool and explore pregnant patients' views on genetic information privacy.</p><p><strong>Methods: </strong>Video education covered prenatal aneuploidy screening and diagnosis and genetic privacy of cell-free DNA (cfDNA). English or Spanish-speaking adult patients, presenting for pregnancy dating ultrasound at a health center or clinic were eligible to answer a demographic questionnaire and view video education. Virtual, in-depth semi-structured interviews were then performed. Thematic analysis of transcripts was performed; all were double coded.</p><p><strong>Results: </strong>Twenty participants completed interviews, achieving data saturation.</p><p><strong>Demographics: </strong>median age 30.5 years, 50% Spanish-speaking, 55% White, 60% Hispanic, 65% had a high-school degree or less, 60% parous. Themes: The intervention was acceptable, accessible, and aided in decision-making. Tangible adjunctive resources were desired. Content misunderstandings included absolute risk of diagnostic testing and perception of aneuploidy as hereditary. Genetic privacy played a minor role in decision-making. Participants were amenable to data-sharing with third parties, but wanted to be informed. They misunderstood that genetic data could never truly be de-identified. No differences were found in opinions on sharing fetal versus maternal data or with academic versus private institutions.</p><p><strong>Conclusion: </strong>Video education was acceptable and comprehensible, yet participants showed limited awareness of cfDNA privacy implications.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503639","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 Diagnosis of Congenital Paraesophageal Hernia With Gastric Volvulus and Postnatal FBN1 Mutation Confirmation.","authors":"Spencer C Darveau, Georges Sylvestre, Sarah J Weingarten","doi":"10.1002/pd.6767","DOIUrl":"https://doi.org/10.1002/pd.6767","url":null,"abstract":"<p><p>We report a case of a fetus with a congenital paraesophageal hernia (CPEH) with suspected volvulus and a paternal history of Marfan syndrome (MFS). The patient was followed by a multidisciplinary team with plans for postnatal surgical intervention and genetic testing. Postnatal examination confirmed CPEH with gastric volvulus, requiring surgical repair on the first day of life. Neonatal genetic analysis detected a paternally inherited heterozygous pathogenic variant in FBN1, associated with MFS. Prenatal ultrasound findings of CPEH and volvulus have seldom been reported as associations with fetal MFS. This case highlights a rare association and the importance of proactive planning and early surgical intervention.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493401","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":"Early-Onset Macrosomia, Advanced Brain Maturation, and Gonadoblastoid Testicular Dysplasia in a Fetus With a PTEN Variant.","authors":"Danielle C Lynch, Anna F Lee, Alison M R Castle","doi":"10.1002/pd.6765","DOIUrl":"https://doi.org/10.1002/pd.6765","url":null,"abstract":"<p><p>We report a case of a male fetus with early-onset macrosomia and a pathogenic variant in PTEN identified on a macrocephaly and overgrowth sequencing panel. The pregnancy ended at 25 weeks gestation. On post-mortem examination, macrosomia was confirmed, and maturation of the brain was approximately 3 weeks ahead of that of the visceral organs. There was microscopic evidence of gonadoblastoid dysplasia, which is an extremely rare finding and has never been associated with PTEN hamartoma tumor syndrome (PHTS). To our knowledge, this is the first report of a prenatal phenotype with a heterozygous germline variant in PTEN.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483606","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":"Strategies to Detect Chromosomal Anomalies Not Identified by NIPT.","authors":"Fergus Scott, May Phoo Han, Ana Elizabeth Gomes de Melo Tavares Ferreira, James Elhindi, Andrew C McLennan","doi":"10.1002/pd.6755","DOIUrl":"https://doi.org/10.1002/pd.6755","url":null,"abstract":"<p><strong>Introduction: </strong>Genome-wide non-invasive prenatal testing (gwNIPT) has screening limitations for detectable chromosomal conditions and cannot detect microdeletions/microduplications (MD) or triploidy. Thickened nuchal translucency (NT) only detects around 10% of these cases.</p><p><strong>Methods: </strong>A 4-year retrospective study of singleton pregnancies undergoing first-line gwNIPT screening with subsequent CVS or amniocentesis. All MD cases, with or without gwNIPT screening, were also analyzed.</p><p><strong>Results: </strong>Among 919 pregnancies with gwNIPT and invasive testing, 338 had a single chromosomal abnormality, with 9 false negative gwNIPT results (2.9%) and 26 undetectable abnormalities (18 MD, 8 triploidy) (7.7%). Twelve cases had a dual chromosomal abnormality and 4 returned a low-risk gwNIPT result. Only three (9%) of the \"missed cases\" had a large NT and two of these also had a structural abnormality. Approximately 90% of chromosomal anomalies missed by gwNIPT were detected by invasive prenatal testing indicated by one or more of the following: failed NIPT (9%), low PAPP-A (12%), early growth restriction (37%) and structural anomalies at pre-NIPT, 13- or 20-week ultrasounds (51%).</p><p><strong>Conclusion: </strong>Most chromosomal abnormalities missed or unable to be found by gwNIPT are detected due to growth restriction or structural anomalies, not an enlarged NT. Failed NIPT and low PAPP-A concentrations contributed to detection.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472934","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":"Management and Outcomes in Isolated Congenital Aqueductal Stenosis: A Single-Center Retrospective Cohort Study.","authors":"Enaja V Sambatur, Shohra Qaderi, Matheus D Soldatelli, Jonathan Castillo, Heidi Castillo, Weston T Northam, Benjamin C Warf, Ramen H Chmait, Eyal Krispin, Patricia Ellen Grant, Alireza A Shamshirsaz","doi":"10.1002/pd.6764","DOIUrl":"https://doi.org/10.1002/pd.6764","url":null,"abstract":"<p><strong>Objective: </strong>Our objective was to investigate prenatal imaging findings, clinical course and outcomes associated with isolated congenital aqueductal stenosis (ICAS).</p><p><strong>Method: </strong>A retrospective study was conducted in the period of 2010-2023, including patients with ICAS confirmed postnatally who were imaged prenatally with ≥ 1 year of follow-up. Patients with additional anomalies (structural or genetic) were excluded. Neurodevelopmental outcomes were verified by pediatricians, and imaging underwent standardized measurement by a neuroradiologist.</p><p><strong>Results: </strong>Twenty-one patients were prenatally diagnosed with ICAS, at a median gestational age (GA) of 19.7 weeks. Overall, 13/14 patients exhibited a fronto-occipital horn ratio (FOHR) > 0.5, indicating clinically significant ventriculomegaly in initial MRI at 18-32 weeks GA. There was an increase in the median size of the third ventricular coronal width from 7 mm in prenatal imaging to 12 mm in postnatal imaging (p = 0.01). Twenty patients (95.2%) required shunting or endoscopic third ventriculostomy and bilateral choroid plexus cauterization (ETV/CPC), with 10 undergoing multiple CSF diversion procedures during follow-up. Among the study group, nine patients experienced epilepsy, 6/8 aged < 5 years exhibited global developmental delay, and 6/12 aged ≥ 5 years required special education services.</p><p><strong>Conclusion: </strong>Our findings indicate a progressive increase in prenatal ventricular sizes, with most children requiring hydrocephalus treatment and experiencing neurodevelopmental impairment.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468779","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}