Elekes Tibor, Ladanyi Aniko, Pap Eva, Szabo Janos, Illes Anett, Gullai Nora, Varbiro Szabolcs
Department of Obstetrics and Gynecology, University of Szeged, H-6725 Szeged, Hungary.
Department of Internal Medicine and Oncology, Semmelweis University, H-1082 Budapest, Hungary.
J Clin Med. 2025 Jun 4;14(11):3973. doi: 10.3390/jcm14113973.
Noonan syndrome (NS) is a relatively common RASopathy that can be associated with a variety of phenotypic and genotypic variations and potential long-term health consequences. Its most described prenatal ultrasound features in the first trimester are thickened nuchal translucency (NT) and dilated jugular sacs; while heart defects, polyhydramnios and facial dysmorphisms are its known manifestations in the second and third trimesters. We present two cases of NS with the prenatal ultrasound diagnosis of external hydrocephalus (EH) in the second trimester. Case 1 had a normal first trimester scan and showed mild polyhydramnios, an echogenic intracardiac focus (EIF) in the left ventricle and pyelectasis in the second trimester in association with the EH. The whole exome sequencing (WES) confirmed a pathogenic variant in the gene. Case 2 showed increased NT, agenesis of the ductus venosus (DV), single umbilical artery (SUA), an EIF in the right ventricle and an abnormal prefrontal space ratio (PSFR). By the 19th gestational week, EH appeared. The ambient and quadrigeminal cisterns were also slightly widened. The WES revealed a gene variant. The most reported sonographic features of NS are either non-specific or difficult to integrate into routine screening, requiring substantial experience. In our two cases, we detected EH in the second trimester, which is rarely described as a prenatal ultrasound diagnosis. To our current knowledge, this is the first case reported of EH in NS caused by an gene variant and these are the first cases reported with the prenatal sonographic diagnosis of EH in NS.
努南综合征（NS）是一种相对常见的RAS病，可伴有多种表型和基因型变异以及潜在的长期健康后果。其在孕早期最常描述的产前超声特征是颈项透明层（NT）增厚和颈静脉囊扩张；而心脏缺陷、羊水过多和面部畸形是其在孕中期和孕晚期的已知表现。我们报告两例在孕中期经产前超声诊断为外部性脑积水（EH）的努南综合征病例。病例1孕早期扫描正常，孕中期显示轻度羊水过多、左心室内有一个心内强回声灶（EIF）和肾盂积水，同时伴有外部性脑积水。全外显子组测序（WES）证实该基因存在一个致病变异。病例2显示NT增加、静脉导管缺如（DV）、单脐动脉（SUA）、右心室内有一个EIF以及前额叶间隙比率（PSFR）异常。到孕19周时，出现了外部性脑积水。环池和四叠体池也略有增宽。WES显示一个基因变异。努南综合征最常报告的超声特征要么是非特异性的，要么难以纳入常规筛查，需要丰富的经验。在我们这两例病例中，我们在孕中期检测到了外部性脑积水，这在产前超声诊断中很少被描述。就我们目前所知，这是首例由基因变异导致努南综合征出现外部性脑积水的病例报告，也是首例有产前超声诊断努南综合征合并外部性脑积水的病例报告。
