Search Results (92)

Background and Clinical Significance: The crista terminalis (CT) is a fibromuscular ridge located on the posterolateral wall of the right atrium, formed by the junction of the sinus venosus and the primitive right atrium. A hypertrophic or prominent CT (HCT) refers to a thickened or conspicuous configuration of this normal anatomical structure. In prenatal ultrasound (US) and/or echocardiographic assessments, HCT can mimic a right atrial mass, such as a tumor or a thrombus. Case Presentation: Herein, we describe a case of a fetal right atrial echogenic mass detected at 32 weeks, which remained stable through gestation and was confirmed postnatally as a likely HCT. No hemodynamic compromise, growth, or pathological sequelae were observed. Conclusions: Our case reinforces the importance of including atrial structural variants in the differential diagnosis of intracardiac masses, particularly when features favor stability and low risk. Serial imaging, avoidance of premature invasive measures, and careful counseling are key to appropriate management. Full article

Background/Objectives: X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare monogenic disorder characterized by hypohidrosis, hypotrichosis, and hypodontia, caused primarily by pathogenic variants in the EDA gene. XLHED predominantly affects males due to its X-linked recessive inheritance, while female carriers may exhibit variable phenotypes due to random X-inactivation. Early diagnosis is critical for timely counseling and emerging therapeutic interventions. We report a rare prenatal diagnosis of XLHED in dizygotic dichorionic male twins during a dichorionic diamniotic pregnancy. At 24 weeks’ gestation, ultrasonographic anomalies—facial dysmorphisms, oligodontia, and hypoechogenic skin—raised suspicion for ectodermal dysplasia. Methods: Non-invasive prenatal test and targeted next-generation sequencing (NGS) of Cell-free DNA identified an hemizygous EDA deletion (c.612_629del; p.Ile205_Gly210del) with 52% variant allele frequency. Results: This in-frame deletion affects a highly conserved region in the TNF homology domain of ectodysplasin-A1, likely compromising protein function. The variant was confirmed in both fetuses via genetic analysis on amniotic fluid and in the heterozygous state in the mother, consistent with X-linked recessive inheritance. Family history revealed a maternal uncle with XLHED. Additional heterozygous variants were also identified in CPT2, GBA1, GJB2, and SMN1 genes. Following comprehensive genetic counseling, the mother opted for abortion. Conclusions: This case underscores the value of applying advanced genomic technologies—cfDNA-based NGS—for prenatal diagnosis of rare genetic disorders. The identification of apathogenic EDA variant expands the mutational spectrum of XLHED and supports early diagnosis for informed reproductive decisions and potential access to emerging prenatal therapies. Broader application of such technologies may improve outcomes in future pregnancies at risk for monogenic disorders. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by the gradual and irreversible loss of neurons, especially within the substantia nigra region of the midbrain. Early and accurate diagnosis remains a significant challenge in both research and clinical practice. This difficulty is further compounded by the substantial clinical and molecular heterogeneity of PD, emphasizing the urgent need for reliable biomarkers to enhance diagnostic precision and guide therapeutic strategies. One promising candidate biomarker is cell-free DNA (cfDNA), comprising short DNA fragments composed of mitochondrial (cf-mtDNA) and nucleus-derived (cf-ntDNA) DNA. cfDNA is released into body fluids through physiological or pathological processes such as apoptosis, necrosis, NETosis, or active secretion. The presence of cfDNA in human biological fluids has been utilized for years in oncology and prenatal medicine and, more recently, it has gained attention as a non-invasive diagnostic tool in the context of neurodegenerative diseases such as PD. This review article aims to provide a comprehensive overview of the current knowledge on the origin of cfDNA, highlighting the roles of the mitochondria and cf-mtDNA in PD, mitochondria quality control, and neuroinflammation in cfDNA biogenesis. The review collates available research on cfDNA types in human serum, plasma, and CSF, sequence analysis, and its potential application as a biomarker in the diagnosis and monitoring of PD, contributing to the ongoing search for non-invasive biomarkers of neurodegenerative diseases. Full article

Background and Clinical Significance: Binder syndrome or maxillonasal dysplasia is a rare developmental disorder affecting the anterior maxilla and nasal complex, characterized by midfacial hypoplasia, a flattened nasal bridge, and increased nasofrontal angle. Case Presentation: We present a case series of seven fetuses diagnosed with Binder phenotype through targeted ultrasound examination at our prenatal diagnosis center during the SARS-CoV-2 pandemic, between September 2021 and July 2023, including the first case described in the literature before 14 weeks. The median gestational age at diagnosis was 21 weeks. Ultrasound features included flattened fetal facial profile, increased nasofrontal angle (>143°), verticalized nasal bones and widened maxillary alveolar arch. Five cases presented as isolated anomalies, while two showed associated findings including growth restriction and polyhydramnios. Invasive prenatal diagnosis was offered in all cases, with three patients consenting to amniocentesis, all revealing normal karyotype and chromosomal microarray. Pregnancy outcomes varied: three patients opted for termination of pregnancy, one case resulted in intrauterine fetal demise, one delivered prematurely with confirmed postnatal phenotype, and two continued pregnancy with normal delivery. Conclusions: This relatively high case frequency within a short timeframe suggests that Binder syndrome, while rare, may not be as uncommon as previously reported. Accurate ultrasound diagnosis combined with comprehensive genetic counseling enables appropriate pregnancy management and optimal perinatal outcomes. Full article

Placenta accreta spectrum (PAS) disorders remain a major cause of maternal morbidity and adverse perinatal outcomes due to abnormal placental adherence and invasion. Early and accurate prenatal diagnosis is essential to optimize surgical planning and reduce complications. Although ultrasound is well established as the cornerstone for PAS detection, the potential role of serial ultrasonography in refining risk assessment and predicting outcomes is increasingly being explored. Monitoring with serial ultrasonographic imaging may offer valuable insights into the progression of sonographic features, such as placental lacunae, myometrial thinning, placental bulge, and bladder wall disruption, which can predict surgical complexity and perinatal risk and influence decision-making and management. However, there is still limited evidence about the prognostic value of serial scans, and the variability in interpreting ultrasound markers continues, presenting challenges. While scoring systems incorporating ultrasound features show promise for risk stratification, further validation in larger studies is needed. Future research should focus on standardizing ultrasound protocols, validating predictive models, and exploring technological innovations, including artificial intelligence, to enhance diagnostic precision. Incorporating serial ultrasound assessments thoughtfully into clinical practice may improve individualized care and outcomes for women affected by PAS, but more studies are required. Full article

Background: Placenta accreta spectrum (PAS) is a serious pregnancy complication associated with significant hemorrhaging and elevated maternal morbidity. Timely prenatal diagnosis is critical for reducing the risk of adverse outcomes. In this study, we aimed to investigate the association between PAS and first-trimester maternal serum screening markers, as well as selected hematological and inflammatory indices, in pregnancies complicated by placenta previa (PP). Methods: A retrospective study was conducted at a tertiary care center. Pregnant women with singleton pregnancies who had been diagnosed with PP and undergone first-trimester aneuploidy screening and delivered at the same institution were included. The participants were divided into two groups: those diagnosed with PAS (including placenta accreta, increta, and percreta) and those with PP without placental invasion. Data on maternal demographics, the first-trimester serum levels of pregnancy-associated plasma protein-A (PAPP-A), and free β-human chorionic gonadotropin (β-hCG), as well as pre-delivery complete blood count parameters, were collected. Associations between these markers and abnormal placental implantation were analyzed. Results: In total, 181 participants were included in this study, corresponding to 15 cases of PAS and 166 cases of non-invasive PP. The women in the PAS group were significantly younger than those in the non-invasive-PP group (25.3 ± 5.1 vs. 30.0 ± 6.3 years, p < 0.001). The serum levels of PAPP-A and free β-hCG were significantly higher in the PAS cases (p < 0.05). The mean platelet volume (MPV) was significantly lower inF the PAS group (p < 0.05). We did not observe any significant differences in other hematological parameters, including hemoglobin concentration, white blood cell count, neutrophil and lymphocyte counts, platelet count, red cell distribution width, and inflammatory ratios such as the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios. Conclusions: Elevated first-trimester levels of PAPP-A and β-hCG, along with a reduced MPV, may serve as early indicators of PAS in pregnancies complicated by PP. These biomarkers may assist in early risk stratification and help inform perinatal management strategies. Full article

Objectives: To evaluate the association between late CVS (placental biopsy, later than 13 weeks of gestations) and complications between sampling and delivery in 8599 cases in the Department of Obstetrics and Gynecology of a private hospital Podobnik, Zagreb, Croatia. Methods: Late chorionic villus sampling under ultrasound guidance was carried out in prospective monocentric cohort study of 7859 (91.4%) cases in the second trimester and 700 (8.6%) cases in the third trimester of pregnancy. Out of 8599 late CVS cases, 1476 (17.2%) were performed because of suspicious ultrasonographic findings. Results: In 43 patients (0.50%), complications were found between sampling and delivery. There were only 12 (0.15%) spontaneous abortions four to six weeks after late CVS (before 28 weeks). We found 190 (2.3%) chromosomal abnormalities. In the group with suspicious ultrasonographic findings, comparing 1476 cases, we found significant oligohydramnios in 375 (25.4%), significant polyhydramnios in 197 (13.3%) and chromosomal abnormalities in 125 (8.5%) cases. Among the 190 patients with chromosomal abnormalities, ultrasonographic findings were detected in 98 (49.2%) after the 22th week of pregnancy. Conclusions: Late CVS is a safe method of invasive prenatal diagnosis with lower spontaneous abortions rate (0.15%). This method, applicable after 13 weeks of gestation, offers a more flexible approach to invasive prenatal diagnosis of chromosome abnormalities, in very specialized fetal-maternal centres for this method. Full article

Spinal muscular atrophy (SMA) is a severe autosomal recessive neuromuscular disorder and a leading genetic cause of infant mortality. Advances in disease-modifying therapies have significantly improved outcomes when treatment is initiated early, underscoring the importance of timely diagnosis. With the growing availability of prenatal genetic screening and high-resolution molecular diagnostics, opportunities for early detection, and potentially in utero intervention, are rapidly expanding. This narrative review synthesizes current evidence on the prenatal management of SMA, focusing on diagnostic strategies, the clinical application of fetal genetic testing, and the emerging potential of fetal therapy. We explore both invasive and non-invasive diagnostic approaches and evaluate experimental prenatal treatment modalities, while critically addressing the associated ethical, regulatory, and economic considerations. As the field progresses, integrating in utero strategies into clinical care may reshape perinatal medicine and offer transformative potential for genetic neurodegenerative disorders diagnosed before birth. The convergence of early diagnosis, fetal intervention, and personalized genetic counseling will be central to optimizing care pathways and outcomes in the era of precision medicine. Although significant challenges remain, the translation of fetal therapy into routine clinical practice is approaching feasibility. Future clinical trials, anchored in definitive prenatal diagnosis, will be essential, with benefits potentially outweighing the inherent procedural risks. Full article

Circulating cell-free nucleic acids (NAs), in particular plasma-derived cell-free DNA, have evolved into promising clinical analytes for prenatal diagnostics, cancer analysis, and cancer surveillance and therapy monitoring. Nevertheless, salivary extracellular and extracellular vesicle (EV)-derived DNA and microRNA have recently gained attention as potential non-invasive biomarkers for a variety of diseases, including cancer, cardiovascular, autoimmune, and infectious diseases. Our goal in this study was therefore to evaluate and optimize commercially available approaches for cell-free nucleic acid isolation, focusing specifically on DNA and miRNA present in cell-free saliva or saliva-derived EVs. Along these lines, we investigated various commercially available kits, which enable parallel isolation of cell-free DNA and RNA in separate fractions from cell-free saliva and salivary EVs, respectively, and compared them to single analyte extraction kits. The efficiency of all tested nucleic acid extraction methods was determined by comparing DNA and RNA fluorescence spectroscopy measurements and quantitative PCR values obtained from a selection of different DNA- and microRNA targets. We found the Norgen Plasma/Serum RNA/DNA Purification Mini kit in combination with the miRCURY exosome isolation kit to work best in our hands and to provide the highest yields of EV-derived nucleic acids. Having tested and identified effective protocols for isolating salivary extracellular nucleic acids, we present with this comparison study, among others, a sound basis for future circulating small nucleic acid and epigenetic biomarker research aiming for early disease diagnosis, prognosis, and prediction from cell-free saliva, representing an easy-to-collect and readily available diagnostic fluid. Full article

The incidence of malignancies diagnosed during pregnancy is estimated at 1 in 1000 pregnancies, with cervical cancer being the most common gynecological malignancy in this population. The increasing maternal age and widespread use of prenatal screening contribute to the rising detection rates. Early symptoms of cervical cancer, such as vaginal bleeding or discharge, often mimic normal pregnancy changes, leading to potential delays in diagnosis. Cervical dysplasia, a known precursor of cervical cancer, is closely associated with high-risk HPV infection, which affects approximately 25% of women of reproductive age. Screening using cytology and HPV testing is considered safe and effective during pregnancy in early detection. Colposcopy remains the gold standard in further diagnostics, with targeted biopsy indicated in selected cases. In cases of high-grade lesions (CIN II/III), conservative management is often preferred, as more than 60% of lesions regress postpartum. Invasive cervical cancer diagnosed during pregnancy is rare, with an estimated incidence of 1.4–4.6 per 100,000 pregnancies. Management decisions depend on gestational age, cancer stage, and the patient’s reproductive preference. Chemotherapy can be administered after the first trimester with acceptable maternal and fetal safety profiles. This review presents current evidence on screening, diagnostic pathways, and treatment strategies. It emphasizes the importance of individualized care, multidisciplinary collaboration, and shared decision-making to optimize outcomes for both mother and fetus. Full article

Background/Objectives: Over the years, the potential of the first-trimester (FT) ultrasound in the detection of fetal structural defects has increased. The main objectives of the first-trimester fetal screening evaluation are the detection of major structural anomalies and the diagnosis of additional sonographic markers for chromosomal disorders. When a fetal anomaly is diagnosed, patients have the right to be informed about the risks, necessary interventions, or alternatives. Depending on the severity of the anomalies and the pregnancy period, the legality of the pregnancy termination was evaluated. The aim of this study was to assess the impact of the first-trimester morphological screening of the fetus using an ultrasound protocol according to the latest international protocols (the ISUOG protocol). Methods: Between 1 January 2024 and 31 December 2024, 854 pregnancies with gestational ages between 11 weeks and 13 weeks + 6 days were morphologically evaluated during the nuchal scan in the Obstetrics and Gynecology Department of the Emergency County Hospital from Craiova. Both transabdominal and transvaginal ultrasound in 2D and in a color Doppler mode were used in the scanning technique. The ultrasound findings were correlated with the genetic testing results and pregnancy outcome. The medical law implications were related to the cases where the ultrasound was performed at about 13 weeks of gestation, and the screening genetic results showed an increased pregnancy risk, which arose during the FT. In these cases, we performed amniocentesis at about 16–17 weeks of gestation, and especially, the Non-Invasive Prenatal Testing (NIPT)-positive cases were confirmed by karyotyping. Still, at this gestational age of diagnosis, the Romanian law would not allow abortions. Results: By using this extended FT ultrasound protocol, we detected 58 cases with fetal structural anomalies. Eighteen cases were also associated with genetic syndromes after performing chorionic villous sampling (CVS). Three cases detected with minor structural anomalies (two cases with club foot and one case with a cleft upper lip) were lost to follow-up. Conclusions: Fetal morphological ultrasound evaluation is feasible in the late first trimester. By using an extended ultrasound protocol, we can detect most of the fetal structural anomalies and contribute to better medical counseling and improve pregnancy outcomes. Full article

Gaucher disease (GD) is the most common lysosomal storage disorder, with an increased prevalence among Ashkenazi Jews. It is an autosomal recessive metabolic disorder caused by pathogenic variants in the GBA1 gene. In this study, we present the case of a 35-year-old patient who initially underwent comprehensive non-invasive prenatal testing (NIPT), which included monogenic disorder screening. The result indicated a very high risk for GD in the fetus. Subsequently, the patient opted for a confirmatory prenatal diagnostic test—prenatal Whole-Exome Sequencing (WES). The results ruled out the diagnosis of GD in the fetus and excluded other genetic disorders included in the panel. This case highlights the importance of confirmatory prenatal testing after a high-risk NIPT and underscores the value of a comprehensive approach, such as WES, in prenatal genetic diagnostics. Full article

Background/Objectives: Non-invasive prenatal testing (NIPT) has become a widely used method for screening common fetal aneuploidies due to its high sensitivity and specificity compared to traditional screening methods. With various NIPT technologies available, such as whole-genome sequencing (WGS), single nucleotide polymorphisms (SNPs), microarray, and rolling circle amplification (RCA), understanding the accuracy and reliability of each method is critical for clinical decision-making. However, comprehensive evaluations comparing the performance of these NIPT methods, especially in terms of predictive values for trisomy detection, remain limited. A systematic review of the difference in accuracy of the different NIPT methods used for common aneuploidy screening. Methods: A systematic review of former clinical studies using different NIPT methods, such as whole-genome sequencing (WGS), a targeted method of single nucleotide polymorphisms (SNPs), microarray and rolling circle amplification (RCA). We collected data from the PubMed, Embase, Web of Science, Scopus, clinicaltrials.gov, and Cochrane library from the last 20 years, between 2003 January and 2023 October, without any language, search filter or publication type restrictions. Results: Two authors selected twenty articles including twenty-one studies to perform the systematic review. In these studies, altogether 92,164 pregnant women were tested by genomics-based non-invasive prenatal testing (NIPT). We extracted data on true positive, false positive, false negative, and true negative values from each study, and calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) from them. We collected data regarding trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13) detection from all studies. Conclusions: As a conclusion, for the detection of common fetal trisomies, different methods of NIPT perform similarly in terms of clinical sensitivity, specificity and NPV. However, the tests utilizing SNP and RCA had lower PPV values than other NIPT methods. Our research indicates all NIPT methods showed greater sensitivity for the detection of T21, above 97%, than traditional screening tests. For T18 detection, the targeted method with the microarray had a lower sensitivity compared to other tests. The SNP and the microarray-based test had high PPV, whilst the other tests, utilizing WGS, and the test with RCA had quite low PPV. Regarding T13 detection, all of the tests performed similarly in terms of clinical sensitivity, specificity, PPV, and NPV (with one exception—one of the tests using WGS had lower PPV). According to these results, there was no significant difference between the methods of NIPT, such as WGS, SNPs, microarray, and RCA, used to detect common trisomies, but the variation in PPV underlines the importance of invasive tests to derive positive NIPT results. We suggest that NIPT combined with US screening for structural abnormalities could further improve the utility of the non-invasive tests in pregnancy. This is the first independent systematic review into the efficacy of the different NIPT methods. Full article

Aneuploidy is increasingly recognized globally as a common cause of miscarriage among expectant mothers. The existing prenatal screening techniques for detecting aneuploidy have several limitations. The ability to diagnose aneuploidy early in a non-invasive manner is not feasible with the current screening methods, as they may produce false positive or false negative results. Recently, the widely used gene editing tool CRISPR/Cas has shown great promise in diagnostics. This review summarizes the prenatal screening tests used in the first trimester to assess aneuploidy conditions. Additionally, we discuss the advantages and disadvantages of molecular diagnostic tests, including the benefits and challenges of CRISPR/Cas-based trisomy detection. Thus, the proposed prenatal screening using CRISPR/Cas could provide significant benefits to expectant mothers by potentially enabling the early diagnosis of trisomy, helping to prevent miscarriage and birth defects. Furthermore, it opens new avenues for research, allowing clinicians and researchers to develop, optimize, and implement CRISPR/Cas-based prenatal screening assays in the future. Full article

Background/Objectives: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by mutations in the CYP21A2 gene associated with 21-hydroxylase deficiency and increased levels of adrenal androgens. Affected females are at risk of ambiguous genitalia, while affected males show sexual precocity. Here, we present a case of a newborn female patient, characterized by ambiguous genitalia and previously identified as low risk for common aneuploidies by non-invasive prenatal testing (NIPT). Methods: We performed a NIPT, which showed a 46, XX genotype, confirmed by karyotype on the newborn’s DNA extracted lymphocytes. For clinical suspicion of CAH, we performed reverse dot blot and Multiple Ligation-dependent Probe Amplification (MLPA) of the CYP21A2 gene on the patients and her parents’ DNA. Then, we performed on mother’s plasma NGS analysis with an in-house developed panel of genes for monogenic diseases, including the CYP21A2 gene. Results: Reverse dot blot and MLPA detected the presence of the c.290-13A/C>G (I2 splice) mutation in heterozygosity in the parents and in homozygosity in the child, respectively. NGS detected the c.290-13A/C>G (I2splice) mutation in cell-free fetal DNA (cfDNA) in mother’s plasma with a variant allele frequency (VAF) of 67% with a fetal fraction (FF) of 5%. This latter suggests the presence of the variant both in the mother and in newborn cfDNA. Conclusions: The study reinforces the hypothesis that cfDNA can be used to identify point mutations, small insertions and/or deletions for the diagnosis of monogenic diseases, reducing the number of invasive tests and the risk of early miscarriages. Early detection of mutations in genes causing sexual development disorders could make it possible to start therapy in the womb. Full article