Prenatal Diagnosis最新文献

Objective: We describe a series of pregnancies with autosomal dominant lymphedema and generalized lymphatic dysplasia in the fetus diagnosed with prenatal exome or genome sequencing. We focus on specific syndromes, fetal features, and parental symptoms to deepen our understanding of congenital lymphatic anomalies.

Methods: Pregnancies with one or more fetal effusions were prospectively enrolled from 2017 to 2024 and underwent exome or genome sequencing. Fetal effusions included increased nuchal translucency ≥ 3.5 mm, cystic hygroma, pleural effusion, pericardial effusion, ascites, and/or skin edema. Records were reviewed to extract personal and family history, ultrasound findings, and pregnancy outcomes.

Results: Among 303 pregnancies with one or more fetal effusions, eight (3%) had a molecular diagnosis of autosomal dominant lymphedema or generalized lymphatic dysplasia. Gestational age at detection of fetal effusion(s) ranged from the first through third trimesters. Four fetuses inherited the genetic variant(s) from a biological parent. Of these, one parent was asymptomatic, and three had largely milder symptoms than their fetus. Perinatal outcomes were more favorable for fetuses with heterozygous PIEZO1 variants.

Conclusion: Autosomal dominant lymphedema and generalized lymphatic dysplasia can present with a breadth of fetal effusions from the first through third trimesters and are frequently inherited from a biological parent with less severe symptoms. These data provide a deeper understanding of how congenital lymphatic anomalies manifest in utero and inform expectations about recurrence risk in future pregnancies.

Objective: Fetal macrocephaly (HC Z-score ≥ +2) is a common reason for referral for neurosonography. While most cases are benign and asymptomatic, syndromic macrocephaly poses a significant risk of abnormal neurodevelopment. This study aimed to describe the sonographic and genetic features of fetuses at the highest risk of syndromic macrocephaly.

Methods: We retrospectively analyzed 19 fetuses with either HC Z-scores ≥ +2.5 or those with ≥ +2 and associated anomalies, evaluated between January 2015 and October 2024. Assessments included fetal neurosonography, anomaly scans, MRI, and genetic work-up. Outcomes and postnatal/postmortem data were reviewed.

Results: Mean gestational age at the time of diagnosis was 29.6 weeks (range 23-35.4 weeks). Seventeen fetuses (89%) had associated anomalies: large for gestational age (12/19), callosal abnormalities (11/19), malformation of cortical development (13/19), and facial dysmorphism (11/19) were diagnosed. Genetic investigation results (CMA) were available for 17 of the 19 patients. Overall, 14 of the 17 patients had abnormal genetic findings, mostly involving mTOR pathway genes.

Conclusion: High Z-scores and additional imaging findings strongly correlate with genetic abnormalities, most often mTOR-related. These results support the integration of exome sequencing into prenatal evaluation of fetal macrocephaly.

Objective: To present prenatal sonographic features, genomic results of chromosomal microarray analysis (CMA) and exome sequencing (ES), and pregnancy outcomes of fetuses with Sotos syndrome, and to provide genetic counseling for at-risk pregnancies.

Methods: This retrospective study analyzed 13 cases of prenatally diagnosed Sotos syndrome from January 2016 to March 2025. We collected and compared ultrasound findings, CMA and ES results, and pregnancy outcomes with the literature.

Results: All 13 cases exhibited de novo abnormalities in the NSD1 gene, with nine deletions identified through CMA and four pathogenic/likely pathogenic variants detected via ES, two of which were novel. The observed phenotypes included increased nuchal translucency (NT) (5/13), central nervous system (CNS) anomalies (6/13), and growth abnormalities (2/13). Additionally, polyhydramnios, cardiac anomalies, and renal anomalies were also noted. All pregnancies resulted in termination.

Conclusion: Sotos syndrome presents with nonspecific symptoms during the early stages of gestation, except for increased NT. However, CNS anomalies begin to appear during the second and third trimesters. Furthermore, polyhydramnios should be noted. A comprehensive prenatal diagnosis of Sotos syndrome can be made through ultrasound and genetic testing.

Objective: Renal cystic dysplasia represents a group of disorders involving primary cilia dysfunction. Autosomal dominant polycystic kidney disease (ADPKD) due to PKD1 pathogenic variants typically presents in adulthood; we investigated rare prenatal-onset cases to better understand their genetic basis and clinical implications.

Method: We performed whole-genome sequencing in trio and long-read sequencing on seven prenatal ADPKD cases. Variant interpretation followed ACMG guidelines, with special consideration for hypomorphic alleles and long-read sequencing for haplotype resolution in some cases.

Results: Our study identified three novel hypomorphic PKD1 variants. Four families showed biallelic inheritance patterns, including one with two affected parents. Despite severe prenatal ultrasound findings, only one case required neonatal dialysis, and all cases lacked oligohydramnios. All other patients revealed no ESKD at the age of diagnosis.

Conclusions: NGS analysis proves essential for diagnosis but requires comprehensive approaches to detect hypomorphic variants and underscores the necessity for comprehensive evaluation of hypomorphic alleles. Our findings demonstrate that prenatal detection does not necessarily predict rapid disease progression, offering new prognostic insights for severe ADPKD presentations that is extremely important for accurate genetic counseling. These results emphasize the need for functional studies of hypomorphic variants while providing a framework for clinical interpretation of early-onset ADPKD cases.

Objective: To provide an updated overview of international clinical practice in prenatal repair of open spinal dysraphism (OSD), focusing on evolving eligibility criteria, surgical techniques, and diagnostic standards.

Methods: A structured online survey was distributed to 83 fetal surgery centers worldwide. The questionnaire addressed surgical techniques, maternal and fetal eligibility and diagnostic standards. Descriptive analyses were performed to identify current trends and practice variations.

Results: 38 centers from 16 countries participated in the survey (response rate 45.8%). Open fetal surgery remains the most common approach (51.4%) though 47.4% reported offering multiple techniques, including fetoscopic methods. Compared with the MOMS criteria, 42.4% performed surgery beyond 25.6 weeks of gestation, 52.4% accepted a BMI 35%-40% and 28.6% acc epted even a BMI of 41%-45%, and 42.4% treated women with prior uterine surgery. Most centers (87.9%) combined ultrasound and MRI for preoperative imaging. Genetic evaluation was heterogeneous: 66.7% required karyotyping, 63.6% required chromosomal microarray, 18.2% non-invasive testing, and 6.1% required none. Prognostic indicators such as ventriculomegaly and motor function increasingly influence selection decisions.

Conclusion: International practice in prenatal OSD repair shows broadening maternal eligibility, diversification of surgical approaches, and variable diagnostic strategies. These findings highlight a shift toward individualised care and emphasise the need for further studies to evaluate the impact of practice adaptations.

Objective: The aim of this study is to evaluate the efficacy of prenatal second trimester ultrasound in diagnosing isolated congenital clubfoot and to assess the role of prenatal genetic testing.

Methods: We conducted a retrospective cohort study in the North-West region of the Netherlands with prenatally suspected clubfoot between 16 and 24 weeks of gestation from 2007 to 2021. We included isolated cases, defined as no additional structural anomalies on the initial targeted ultrasound. Rapid aneuploidy testing, chromosomal microarray analysis, and/or exome sequencing were performed via invasive testing following on parental request.

Results: We identified 423 cases of isolated clubfoot. The diagnosis changed to prenatal non-isolated clubfoot during prenatal follow-up in 20 cases (5%); in 10 cases during a follow-up ultrasound, and in 10 cases, an underlying genetic condition was found. In 11 cases, the initial suspicion of clubfoot was not confirmed at follow-up ultrasound. There were 387 ongoing pregnancies with a prenatal diagnosis of isolated clubfoot. In 47 children (12%), diagnosis changed postnatally to non-isolated. These postnatal findings were classified as major in 36 children (9%). In 40 cases (10%), the prenatal diagnosis of clubfoot was not confirmed postnatally.

Conclusion: Prenatal ultrasound combined with genetic testing are components in the work-up of clubfoot, enabling the identification of associated structural anomalies and underlying genetic disorders. Despite advances in prenatal ultrasound and genetic testing, distinguishing isolated clubfoot from cases with additional structural or genetic anomalies remains challenging. Moreover, prenatal genetic testing does not exclude the absence of structural or neurodevelopmental issues diagnosed after birth.

Objective: This study aimed to evaluate the sonographic features of giant fetal hepatic hemangioma (GFHH) as predictors of complications and outcomes.

Methods: We conducted a retrospective analysis of prenatally diagnosed GFHH cases between 2014 and 2024, reviewing ultrasonographic features, complications, and neonatal outcomes.

Results: Among 36 fetuses, 38.9% exhibited homogeneous masses and 61.1% showed heterogeneous masses. Peripheral annular or semi-annular blood flow was observed in 88.9% of cases. Heterogeneous echogenicity was more frequent in the complicated group (93.3%, 14/15) than in the uncomplicated group (38.1%, 8/21) (p < 0.01). Significant differences were identified between the complicated and uncomplicated groups regarding the presence of vascularity, arteriovenous fistula (AVF), hepatic artery peak systolic velocity (HAPSV) (> 106 cm/s), and hepatic vein dilation (≥ 3 veins) (all p < 0.05). The survival rate was 100% among the 21 fetuses in the uncomplicated group, compared with 73.3% among the 15 fetuses in the complicated group.

Conclusion: The typical presentation of GFHH is a well-defined hypoechoic mass with peripheral circular or semicircular vascularity. Homogeneous masses are predictive of favorable outcomes, whereas within heterogeneous masses, features such as hypervascularity, AVF, HAPSV > 106 cm/s, and dilation of three hepatic veins are closely correlated with an increased risk of complications.

The main objective of our study was to conduct a systematic literature review and a meta-analysis to evaluate the incremental yield of chromosomal microarray analysis compared with karyotyping in cases of fetal growth restriction. Our review was designed according to the PRISMA guidelines. It included all observational studies that reported the results of CMA testing in fetuses diagnosed with growth restriction without additional findings (isolated FGR), with structural abnormalities (malformed FGR) and with the presence of additional findings that would not qualify as structural abnormalities (nonmalformed FGR). The study included 22 studies with a total of 2275 cases of affected fetuses that met the inclusion criteria for analysis. Combined data from these studies revealed an overall 3% incremental yield of CMA over karyotyping (95% CI 2%-5%) in isolated cases, an overall 4% incremental yield of CMA over karyotyping (95% CI 3%-5%) in nonmalformed FGR cases and an overall 10% incremental yield (95% CI -13%) in malformed FGR cases. Our findings may be useful in clinical practice to guide management options and the counseling of the couples to individualize patient care and facilitate clinicians when they come across such a common clinical entity.