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This case report describes a fetus in which HRV was identified by first-trimester ultrasound at 12+4 weeks after an initially normal genome-wide cell-free DNA screen. Rapid exome sequencing confirmed a de novo heterozygous SMAD2 loss-of-function variant (c.388C>T, p.(Arg130Ter)), later confirmed at autopsy. The authors emphasize early detection enables timely genetic testing and pregnancy management.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/hypoplastic-right-ventricle-caused-by-a-novel-smad2-variant-identified-in-the-first-trimester-a-case-report/417282/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/hypoplastic-right-ventricle-caused-by-a-novel-smad2-variant-identified-in-the-first-trimester-a-case-report/417282.png","ImageObject",300,407,{"name":92,"@type":93},"hdkawk","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is hypoplastic right ventricle (HRV) and why is it rare?","Question",{"text":112,"@type":113},"HRV refers to pulmonary atresia with intact ventricular septum and involves significant obstruction of the right ventricular outflow tract, interfering with right ventricle development. It is described as extremely rare.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the SMAD2 variant identified in this case?",{"text":117,"@type":113},"The fetus underwent chorionic villus sampling and rapid exome sequencing. The sequencing detected a de novo heterozygous SMAD2 variant c.388C>T, p.(Arg130Ter), which was not found in either parent.",{"name":119,"@type":110,"acceptedAnswer":120},"Why did the authors use exome sequencing instead of microarray?",{"text":121,"@type":113},"Because the genome-wide cell-free DNA screen was negative prior to first-trimester ultrasound, the authors concluded the fetus had a higher risk for single-gene disorders than chromosomal abnormalities. Exome sequencing was therefore used as the first-tier genetic test.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},417282,1791092878,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":24,"preview_page_count":4},3985747859855,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","| Research Letter |\n| --- |\n|  |\n\nHypoplastic Right Ventricle Caused by a Novel SMAD2 Variant Identified in the First Trimester: A Case Report  \nYan‑Dong Yang1,2, Dong‑Zhi Li3*  \n1Department of Ultrasound, The Sixth Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong, China, 2Biomedical lnnovation Center, The Sixth Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong, China, 3Department of Prenatal Diagnosis, Guangzhou Women and Children’s Medical Center, Guangzhou  \nMedical University, Guangzhou, Guangdong, China  \nDear Editor,  \nHypoplastic right ventricle (HRV), also referred as pulmonary atresia with intact ventricular septum, is extremely rare, involving a significant obstruction of the right ventricular outflow tract and interfering with adequate development of the right ventricle.[1] Fetal cardiac anomalies are typically detected by second‑trimester anomaly ultrasound performed between 18 and 22 weeks. We here report a fetal case of HRV caused by aSMAD2 variant, which was identified by ultrasound in the first trimester.  \nA32‑year‑old primigravida woman had a normal genome‑wide cell‑free DNA aneuploidy screening at 9 weeks’ gestation. At 12 + 4 weeks, the routine first‑trimester ultrasound revealed a normal nuchal translucency measurement of 1.5 mm, but a single ventricle of the heart [Figure 1a andb]. Chorionic villus sampling was performed, and rapid exome sequencing was used for genetic testing. The Illumina HiSeq2500 Analyzer platform (Illumina, San Diego) was used to obtain a mean sequencing coverage of more than 90×, with more than 98% of the target bases having at least ×20 coverage. At 14 + 4 weeks, a follow‑up ultrasound achieved the diagnosis of HRV [Figure 1c‑e] . Theexome sequencing detected a de novo heterozygous variant c.388C>T, p.(Arg130Ter) in the SMAD2 gene which was not identified in both parents [Figure 1f]. Loss‑of‑functionSMAD2 variants cause a wide spectrum of autosomal‑dominant aortic and arterial aneurysmal disease, complex congenital heart diseases (CHD), and neurodevelopmental disability.[2]  \nAfter genetic counseling, the couple opted for pregnancy termination at 15 weeks. Fetal autopsy confirmed the HRV with pulmonary and tricuspid atresia, but with intact ventricular septum. The aortic root, ascending aorta, aortic arch, descending aorta, and the abdominal part of the aorta seemed normal at this fetal stage.  \nReceived: 13‑08‑2024 Revised: 02‑09‑2024 Accepted: 10‑09‑2024 Available Online: 10‑03‑2025  \n\n| Access this article online |  |\n| --- | --- |\n| Quick Response Code:\u003Cbr>| Website:\u003Cbr>[https://journals.lww.com/jmut](https://journals.lww.com/jmut) |\n|  | DOI:\u003Cbr>10.4103/jmu.jmu_ 103_24 |\n\nThe involved CHD types associated with SMAD2 variants include cardiac septal defects, double‑outlet right ventricle, unbalanced complete atrioventricular canal, valvular anomalies, dextroposition of the great arteries, anomalous pulmonary venous return, and superior vena cava to the left atrium defect. [3] We first report HRV as the cardiovascular phenotype associated with SMAD2 pathogenic variants.  \nIn our case, the left ventricle supplies both systemic and pulmonary circulations, the latter reflected by retrograde flow through the ductus arteriosus. We determined the diagnosis of HRVat 14 + 4 weeks’gestation, but it behaved as a univentricular heart on the 12‑week ultrasound. In a study of 7167 low‑risk cases, Bottelli et al.[4] reported that 7/12 fetuses of major CHDs were detected on first‑trimester ultrasound (crown‑rump length, 50.1–84.0 mm), corresponding to a sensitivity of 58.3% . In a systematic review and meta‑analysis, Karim et al.[5] reported that first‑trimester ultrasound had a pooled sensitivity of 55.80% in 1445 major cardiac anomalies in thenonhigh‑risk population, with a sensitivity of 91.7% for hypoplastic right heart syndrome. Therefore, as evidencedby our report, first‑trimester ultrasound allows the identification of major cardiac pathology, which gives","cbCaicxJbmq04G0i","https://ap.wps.com/l/cbCaicxJbmq04G0i","pdf",664584,"English","# Case report\n## Ultrasound findings\n## Genetic testing and follow-up\n## Pregnancy outcome and autopsy\n## Clinical significance","[{\"question\":\"What is hypoplastic right ventricle (HRV) and why is it rare?\",\"answer\":\"HRV refers to pulmonary atresia with intact ventricular septum and involves significant obstruction of the right ventricular outflow tract, interfering with right ventricle development. It is described as extremely rare.\"},{\"question\":\"How was the SMAD2 variant identified in this case?\",\"answer\":\"The fetus underwent chorionic villus sampling and rapid exome sequencing. The sequencing detected a de novo heterozygous SMAD2 variant c.388C\\u003eT, p.(Arg130Ter), which was not found in either parent.\"},{\"question\":\"Why did the authors use exome sequencing instead of microarray?\",\"answer\":\"Because the genome-wide cell-free DNA screen was negative prior to first-trimester ultrasound, the authors concluded the fetus had a higher risk for single-gene disorders than chromosomal abnormalities. Exome sequencing was therefore used as the first-tier genetic test.\"}]","Hypoplastic Right Ventricle Caused by a Novel SMAD2 Variant Identified in the First Trimester - A Case Report | PDF",1790608693]