Ultrasound Anomalies Research Articles

Incidence of chromosomal abnormalities in fetuses with first trimester ultrasound anomalies and a low-risk cell-free DNA test for common trisomies.

To examine the incidence and type of chromosomal abnormalities in fetuses with first trimester ultrasound anomalies and a low-risk cfDNA test for common trisomies. In 486 singleton pregnancies undergoing invasive testing after combined screening, a detailed first trimester ultrasound assessment was carried out and a maternal blood sample was sent for cfDNA analysis. Ultrasound and cfDNA data were analyzed in relation to fetal karyotype. Invasive testing demonstrated a chromosomal abnormality in 157 (32.3%) of 486 fetuses. In 348 cases with a low-risk cfDNA test for common trisomies, NT ≥ 3.5 mm and/or a major structural defect were observed in 92 (26.4%) fetuses. A chromosomal abnormality was found in 17 (18.5%; 95%CI 10.55-26.41) of these pregnancies, including 1 (1.1%) case of trisomy 21 and 16 (17.4%) fetuses with abnormalities different from common trisomies. The respective incidence in the 256 cases with a low-risk cfDNA test result and no ultrasound anomalies was 2.3% (95% CI 0.49-4.20; n = 6). In fetuses with first trimester ultrasound anomalies and a low-risk cfDNA result for trisomy 21, 18 and 13, diagnostic testing should be offered with the main objective to detect chromosomal abnormalities beyond common trisomies.

Chromosome microarray analysis should be offered to all invasive prenatal diagnostic testing following a normal rapid aneuploidy test result.

Chromosomal microarray analysis (CMA) has now replaced karyotyping in the analysis of prenatal cases with a fetal structural anomaly, whereas in those pregnancies undergoing invasive prenatal diagnosis with a normal fetal ultrasound, conventional karyotyping is still performed. The aims of this study were to establish the diagnostic yield of CMA in prenatal diagnosis, and to provide new data that might contribute to reconsider current practices. We reviewed 2905 prenatal samples with a normal rapid aneuploidy detection test referred for evaluation by CMA testing. Our study revealed pathogenic and reported susceptibility copy number variants associated with syndromic disorders in 4.8% (n = 138/2905) of cases, being 2.8% (n = 81/2905) the estimated added diagnostic value of CMA over karyotyping. Clinically significant CMA abnormality was detected in 5.4% (107/1975) of the fetuses with ultrasound anomalies and in 1.4% (5/345) of those considered as low-risk pregnancies. Our series shows that in prenatal samples, CMA increases 2-fold the diagnostic yield achieved by conventional karyotyping.

Ultrasound features of fetal toxoplasmosis: A contemporary multicenter survey in 88 fetuses.

To describe the lesions detected by prenatal ultrasound examination in congenital toxoplasmosis (CT). We retrospectively analyzed all cases of fetal infection with Toxoplasma gondii with ultrasound anomalies described by fetal medicine experts in 2009 to 2019 in 30 French centers. Eighty-eight cases of CT were included. Forty-five (51.1%) had one or more cerebral signs only, 35 (39.8%) had cerebral plus extracerebral signs and 8 (9.1%) had extracerebral signs only. The main cerebral signs were intracranial hyperechogenic nodular foci (n = 60) of which 20 were isolated, ventriculomegalies (n = 44) which generally increased during follow-up, and periventricular abscesses (n = 12). The main extracerebral signs were hepatomegaly and/or splenomegaly (n = 14), small for gestational age (n = 14), ascites (n = 14, including 2 with hydrops), and hyperechogenic bowel (n = 11). Maternal infection occurred mostly in the first or second trimester (81 cases), periconceptionally in one and in the third trimester in six cases. The first ultrasound signs were detected after a median of 7 weeks (range: 1.4; 24.0) following maternal toxoplasmosis seroconversion. While no sign was specific of CT, there were typical associations of cerebral signs with or without extracerebral signs. Detailed ultrasound examination could improve prognostic evaluation, as well as diagnosis of CT in settings lacking serological screening.

The use of fetal exome sequencing in prenatal diagnosis: a points to consider document of the American College of Medical Genetics and Genomics (ACMG)

The use of fetal exome sequencing in prenatal diagnosis: a points to consider document of the American College of Medical Genetics and Genomics (ACMG)

Comparison of Fetal Echocardiography for Fetal Cardiac Structure in Women with Gestational Diabetes Mellitus and Normal Pregnancies

BackgroundIncreased metabolic rate of hyperglycemia in gestational diabetes causes macrosomia, which can also affect the fetal heart. The thickness of the walls of the heart and its function in women with gestational diabetes mellitus (GDM) can change over time before treatment. We aimed to evaluate fetal cardiac structure in terms of ventricular wall thickness and its function in women with GDM and normal pregnancy for indirect evaluation of the effects of hyperglycemia on the heart.Materials and MethodsIn this case-control study, pregnant women who referred to Imam Khomeini hospital, Ahvaz, Iran that had normal ultrasound anomaly scan between the ages of 18 to 22 weeks; in 26-28 weeks of pregnancy using 3-hour glucose tolerance test, based on the results were divided into two groups of gestational diabetes (cases, n=45), and normal (control, n=48 group). Fetal echocardiography was performed between the ages of 28 to 32 weeks and the thickness of the ventricular and inter-ventricular septum and the shortening fraction were compared. ResultsNinety-three pregnant women were participants. The mean age of the subjects was 26.33+ 4.88 years. There was a significant and direct relationship between right ventricular wall thickness, left ventricular thickness and intra ventricular septum, besides, right ventricular fractional shortening increased significantly in the diabetes group compared to the normal pregnancy group (P< 0.05); however, there was no significant difference in left ventricular function between the two groups.ConclusionBased on the results, significant increases in the right ventricular wall thickness, left ventricular thickness and intra ventricular septum, as well as right ventricular fractional shortening; which points to the importance of fetal echocardiography in GDM.

Cost-effectiveness analysis of chromosomal microarray as a primary test for prenatal diagnosis in Hong Kong

BackgroundChromosomal microarray (CMA) has been shown to be cost-effective over karyotyping in invasive prenatal diagnosis for pregnancies with fetal ultrasound anomalies. Yet, information regarding preceding and subsequent tests must be considered as a whole before the true cost-effectiveness can emerge. Currently in Hong Kong, karyotyping is offered free as the standard prenatal test while genome-wide array comparative genome hybridization (aCGH), a form of CMA, is self-financed. A new algorithm was proposed to use aCGH following quantitative fluorescent polymerase chain reaction (QF-PCR) as primary test instead of karyotyping. This study aims to evaluate the cost-effectiveness of the proposed algorithm versus the current algorithm for prenatal diagnosis in Hong Kong.MethodsBetween November 2014 and February 2016, 129 pregnant women who required invasive prenatal diagnosis at two public hospitals in Hong Kong were prospectively recruited. The proposed algorithm was performed for all participants in this demonstration study. For the cost-effectiveness analysis, cost and outcome (diagnostic rate) data were compared with that of a hypothetical scenario representing the current algorithm. Further analysis was performed to incorporate women’s willingness-to-pay for the aCGH test. Impact of government subsidies on the aCGH test was explored as a sensitivity analysis.ResultsThe proposed algorithm dominated the current algorithm for prenatal diagnosis. Both algorithms were equally effective but the proposed algorithm was significantly cheaper (p ≤ 0.05). Taking into account women’s willingness-to-pay for an aCGH test, the proposed algorithm was more effective and less costly than the current algorithm. When the government subsidy reaches 100%, the maximum number of diagnoses could be made.ConclusionBy switching to the proposed algorithm, cost saving can be achieved whilst maximizing the diagnostic rate for invasive prenatal diagnosis. It is recommended to implement aCGH as a primary test following QF-PCR to replace the majority of karyotyping for prenatal diagnosis in Hong Kong.

Prenatal findings, neonatal symptoms and neurodevelopmental outcome of congenital cytomegalovirus infection in a university hospital in Montreal, Quebec.

Background Outcome of congenital cytomegalovirus (cCMV) infection in the absence of routine CMV screening and third-trimester scan in North America is scarcely documented. The aim of this study was to assess the severe outcomes related to cCMV according to the indication for screening. Methods This was a retrospective study of 84 mother-child pairs followed for cCMV between 2003 and 2017 at CHU Sainte-Justine in Montreal, Canada. Prenatal ultrasound, neonatal symptoms, neuroimaging and severe outcomes (cerebral palsy, severe cognitive impairment, bilateral hearing loss or neonatal death) were reviewed. Results Among 38 cases with abnormal prenatal ultrasound, 41.9% of live-born infants developed severe outcomes. Sixteen (42.1%) were detected in the third trimester. Among 16 cases diagnosed prenatally because of maternal history, all had normal prenatal ultrasound, and none developed severe outcomes. Among cases diagnosed postnatally because of neonatal symptoms, 25% developed severe outcomes. All infants who developed severe outcomes had moderate/severe neonatal symptoms. Conclusion Outcome of cCMV infection varies according to the reason for screening and timing of diagnosis. Any prenatal ultrasound anomaly might indicate a risk of severe outcome, and warrants a detailed ultrasound scan. However, late detection, or postnatal diagnosis, represented more than half of the cases, and awareness of this will help ensuring optimal management.

Exome Sequencing for Prenatal Detection of Genetic Abnormalities in Fetal Ultrasound Anomalies: An Economic Evaluation

Introduction: In light of the prospective Prenatal Assessment of Genomes and Exomes (PAGE) study, this paper aimed to determine the additional costs of using exome sequencing (ES) alongside or in place of chromosomal microarray (CMA) in a fetus with an identified congenital anomaly. Methods: A decision tree was populated using data from a prospective cohort of women undergoing invasive diagnostic testing. Four testing strategies were evaluated: CMA, ES, CMA followed by ES (“stepwise”); CMA and ES combined. Results: When ES is priced at GBP 2,100 (EUR 2,407/USD 2,694), performing ES alone prenatally would cost a further GBP 31,410 (EUR 36,001/USD 40,289) per additional genetic diagnosis, whereas the stepwise would cost a further GBP 24,657 (EUR 28,261/USD 31,627) per additional genetic diagnosis. When ES is priced at GBP 966 (EUR 1,107/USD 1,239), performing ES alone prenatally would cost a further GBP 11,532 (EUR 13,217/USD 14,792) per additional genetic diagnosis, whereas the stepwise would cost a further additional GBP 11,639 (EUR 13,340/USD 14,929) per additional genetic diagnosis. The sub-group analysis suggests that performing stepwise on cases indicative of multiple anomalies at ultrasound scan (USS) compared to cases indicative of a single anomaly, is more cost-effective compared to using ES alone. Discussion/Conclusion: Performing ES alongside CMA is more cost-effective than ES alone, which can potentially lead to improvements in pregnancy management. The direct effects of test results on pregnancy outcomes were not examined; therefore, further research is recommended to examine changes on the projected incremental cost-effectiveness ratios.

Laparoscopy-assisted transumbilical extracorporeal cyst deroofing for the management of neonatal ovarian cysts

Background Congenital ovarian cysts affect newborn female infants with an increasing incidence. Many of these cysts are clinically insignificant and resolve spontaneously. Complex cysts of any size and simple cysts larger than 5 cm should be operated upon. Laparoscopy is becoming the mainstay of management. We report our experience with the laparoscopy-assisted transumbilical extracorporeal approach in neonates with ovarian cysts. Patients and methods In this prospective cohort study, 17 pregnant ladies presented with a routine antenatal ultrasound anomaly scan showing an abdominal cyst in their female fetuses, likely ovarian in origin. A multidisciplinary counseling meeting was conducted with the expectant couple. Postnatal ultrasonography confirmed the diagnosis in 15 patients, whereas two patients showed resolution. Conservative management was pursued in patients with cyst size less than 5 cm. Patients with ovarian cysts larger than 5 cm were operated upon electively. Results Age at surgery ranged from 4 to 11 days, and patients’ weight ranged from 2.8 to 3.7 kg. Thirteen patients were full term, whereas only two were preterm. The cyst diameter (whether operated upon or not) ranged from 2.7 to 6.2 cm. All patients with cysts smaller than 5 cm resolved spontaneously over a 6-month period. Laparoscopy-assisted transumbilical extracorporeal cyst deroofing was attempted in 11 patients (mean cyst diameter, 5.6 cm). The mean operative time was 36 min. None of the patients showed recurrence or formation of new cysts. Conclusion Laparoscopy-assisted transumbilical extracorporeal cyst deroofing achieves safety, reproducibility, organ preservation, and minimal invasiveness in neonates with ovarian cysts.

Chromosomal microarray analysis for pregnancies with or without ultrasound abnormalities in women of advanced maternal age.

BackgroundChromosomal microarray analysis (CMA) has been suggested to be routinely conducted for fetuses with ultrasound abnormalities (UA), especially with ultrasound structural anomalies (USA). Whether to routinely offer CMA to women of advanced maternal age (AMA) without UA when undergoing invasive prenatal testing is inconclusive.ObjectiveThis study aimed to evaluate the efficiency of CMA in detecting clinically significant chromosomal abnormalities in fetuses, with or without UA, of women with AMA.MethodsData from singleton pregnancies referred for prenatal CMA due to AMA, with or without UA were obtained. The enrolled cases were divided into AMA group (group A) and AMA accompanied by UA group (group B). Single nucleotide polymorphism (SNP) array technology and conventional karyotyping were performed simultaneously.ResultsA total of 703 cases were enrolled and divided into group A (N = 437) and group B (N = 266). Clinically significant abnormalities were detected by CMA in 52 cases (7.4%, 52/703; the value in group A was significantly lower than that in group B (3.9% vs 13.2%, P < .05); no statistic difference was observed with respect to submicroscopic variants of clinical significance between the two groups (0.9% vs 2.6%, P > .05).ConclusionsChromosomal microarray analysis should be available to all women with AMA undergoing invasive prenatal testing, regardless of ultrasound findings.

Outcome of non-visualization of fetal gallbladder on second-trimester ultrasound: cohort study and systematic review of literature.

To investigate the ultrasound characteristics and outcome of fetuses with non-visualization of the fetal gallbladder (NVFGB) followed in our tertiary university hospital, and to provide a comprehensive review of the literature on prenatal findings and outcome of NVFGB. NVFGB was defined as non-visualization of the gallbladder on two targeted ultrasound examinations performed within a 1-week period. First, we reviewed the medical records of NVFGB cases managed in our center over a 9-year period. Then, we performed a systematic review of the literature to identify studies on NVFGB. The incidence of chromosomal anomalies, later visualization of the gallbladder, gallbladder agenesis, cystic fibrosis and biliary atresia was assessed in fetuses with isolated and non-isolated NVFGB. The role of hepatic enzyme measurements in the diagnosis of cystic fibrosis and biliary atresia in fetuses with NVFGB was also reviewed. Sixteen cases of NVFGB were followed in our center, in 10 (62.5%) of which it was an isolated finding. The incidence of biliary atresia was 12.5% and that of gallbladder agenesis was 12.5%, while no case of cystic fibrosis was reported. The gallbladder was visualized later in pregnancy or postnatally in 43.8% and 25.0% of cases, respectively. A total of seven studies, including our cohort, involving a total of 280 NVFGB cases, met the inclusion criteria for the systematic review. Overall, 20.5% of fetuses had an associated ultrasound anomaly, and the incidence of chromosomal anomaly in this group was 20.4%. In cases with isolated NVFGB, the incidence of chromosomal anomaly was 1.9%. In fetuses with normal karyotype and isolated NVFGB, the gallbladder was later visualized in 70.4% of cases, while the incidence of gallbladder agenesis, cystic fibrosis and biliary atresia was 25.2%, 3.1% and 4.8%, respectively. In fetuses with non-isolated NVFGB, the incidence of cystic fibrosis and biliary atresia was 23.1% and 18.2%, respectively. The negative predictive value of amniotic fluid enzyme levels for the prediction of severe disease (including biliary atresia or cystic fibrosis) ranged between 94% and 100% when evaluated before 22 weeks' gestation, and dropped to 88% after 22 weeks. In cases with persistent NVFGB, the risk of a severe postnatal condition should be considered. A detailed ultrasound scan should be offered and parents tested for cystic fibrosis gene mutation. An invasive procedure for karyotyping and measurement of liver enzyme concentrations before 22 weeks constitutes a reasonable work-up. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal diagnosis of micrognathia in 41 fetuses: Retrospective analysis of outcome and genetic etiologies

Fetal micrognathia can be detected early in pregnancy. Prognosis of micrognathia depends on the risk of respiratory distress at birth and on the long-term risk of intellectual disability. The purpose of this study was to evaluate the long-term prognosis of fetuses with prenatal diagnosis of micrognathia by estimating the prevalence and the severity of confirmed genetic diagnosis in our cohort. Our retrospective study included 41 fetuses with prenatal diagnosis of micrognathia referred to the multidisciplinary centers for prenatal diagnosis in Nice and Marseille, France, between 2006 and 2016. Fetal micrognathia was associated with cleft palate in 27 cases. A genetic cause was confirmed in 21 cases (67%). A chromosomal abnormality was present in 12 cases, including three copy-number variations diagnosed by array CGH. Monogenic disorders were identified in nine cases, most often after birth. Fetuses with family history of micrognathia or Pierre Robin sequence had a favorable outcome. Prognosis was good for the fetuses without associated findings and normal chromosomal analysis, with the exception of one case with a postnatal diagnosis of mandibulofacial dysostosis with microcephaly. Prognostic was poor for the fetuses with additional ultrasound anomalies, as only 5 out of 28 children had a good outcome. Prenatal diagnosis of micrognathia is an indicator of a possible fetal pathology justifying multidisciplinary management. Our study confirms the necessity of performing prenatal array CGH. Use of high-throughput gene sequencing in prenatal period could improve diagnostic performance, prenatal counseling, and adequate postnatal care.

Prenatal diagnosis of chromosomal aberrations by chromosomal microarray analysis in fetuses with ultrasound anomalies in the urinary system.

This study aimed to explore the relationships between urinary anomalies and copy number variations (CNVs) in fetuses and provide information for prenatal diagnosis and genetic counseling for parents. Three hundred seventeen fetuses with urinary system anomalies detected by prenatal ultrasound were enrolled; 251 had isolated urinary system anomalies, and 66 had nonisolated system anomalies. CMA was performed on the Affymetrix 750K platform. The frequency of chromosomal aberrations in fetuses with urinary system anomalies was 11.04%, including 6.31% with pathogenic CNVs (pCNVs). The detection rate of chromosomal abnormalities was significantly higher for the fetuses with nonisolated urinary system anomalies than for those with isolated urinary system anomalies. Seven fetuses (25.93%) with echogenic kidneys were identified with pCNVs; this detection rate was significantly higher than that for fetuses with other urinary anomalies. A 17q12 deletion was detected in eight fetuses with urinary anomalies, accounting for 40% of pCNVs. CMA is especially valuable in the prenatal diagnosis of fetuses with urinary system anomalies. The pCNV rates differed between the isolated and nonisolated subgroups of urinary anomalies. Fetuses with echogenic kidneys had the highest rate of pCNVs. The 17q12 deletion was the most frequent pCNV in fetuses with urinary anomalies.

Prenatal diagnosis of Pallister-Killian syndrome using cord blood samples

BackgroundPallister-Killian syndrome (PKS) (OMIM:#601803) is a rare sporadic genetic disorder characterized by multi-malformations which is caused by the presence of the extra isochromosome 12p. PKS is featured by the tissue-limited mosaicism of the isochromosome 12p [i(12p)]. There were a wide spectrum of prenatal ultrasound findings of PKS, which made it difficult to be found in first or second trimester. Polyhydramnios, diaphragmatic hernia, and rhizomelic limb shortening were the most common prenatal ultrasound abnormalities in PKS. This study retrospectively analyzed the ultrasound findings and molecular cytogenetic results of four PKS fetuses diagnosed by using cord blood samples.ResultsThe ultrasound anomalies of four PKS fetuses are described as follows: fetal macrosomia, cerebral ventriculomegaly, increased NT thickness, rhizomelic limbs shortening, polyhydramnios. Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL) measurements were above the mean in three fetuses,while one fetus showed rhizomelic limbs shortening. Combined with this study and previous literature, polyhydramnios was the most frequent anomaly observed in prenatal ultrasound examination of PKS, which accounted for 48% (94/194). Fetal macrosomia was present in 15% (29/194), cerebral ventriculomegaly in 13% (25/194), thickened nuchal fold in 9% (18/194), rhizomelic limbs shortening in 26% (51/194). I(12p) was found in the karyotype analysis of cultured cord blood lymphocytes and the mosaic ratios ranged from 2 to 5%. Single nucleotide polymorphisms array (SNP-array) results suggested that the whole short arm of chromosome 12 was duplicated with 2~3 copies. Fluorescence in situ hybridization (FISH) was performed to confirm the results of karyotype and SNP-array.ConclusionsIn case non-specific indicators such as fetal macrosomia, polyhydramnios and rhizomelic limbs shortening are observed meanwhile in prenatal ultrasound, targeted detection of PKS should be considered. In the prenatal diagnosis of PKS, the combination of SNP-array and FISH with conventional karyotype are the key to seek i(12p) and for precise diagnosis.

Is an analysis of copy number variants necessary for various types of kidney ultrasound anomalies in fetuses?

BackgroundThis study aimed to estimate the associations of copy number variants (CNVs) with fetal kidney ultrasound anomalies. A total of 331 fetuses with kidney ultrasound anomalies who underwent prenatal chromosomal microarray analyses were enrolled. The fetuses were classified into groups with isolated and nonisolated anomalies or according to the types of kidney anomalies.ResultsClinically significant CNVs were identified in 3.4% or 7.3% of fetuses with isolated or nonisolated kidney anomalies, respectively. CNVs were more frequently identified in fetuses with abnormal embryonic migration of the kidneys (6.6%) than in fetuses with malformations of the renal parenchyma (4.7%) or anomalies of the urinary collecting system (3.4%). In particular, CNVs were most frequently detected in fetuses with ectopic kidneys (9.5%) but not in fetuses with horseshoe kidneys or isolated duplex kidneys. Among these CNVs, the most common were del(17)(q12q12) (1.2%) and del(22)(q11q11) (0.6%). The dup(17)(p12p12) and del(15)(q11.2q11.2) CNVs were identified in this study but not in previous studies. The del(X)(p11.4p11.4) and del(16)(p13.3p13.3) CNVs were further implicated as associated with kidney anomalies.ConclusionsFetuses with abnormal embryonic migration of the kidneys (particularly ectopic kidneys) showed a higher frequency of clinically significant CNVs, whereas fetuses with horseshoe kidneys or duplex kidneys were less frequently associated with these CNVs.

Fetal megacystis: a lot more than LUTO.

ABSTRACTObjectiveFetal megacystis presents a challenge in terms of counseling and management because of its varied etiology and evolution. The aim of this study was to present a comprehensive overview of the underlying etiologies and structural anomalies associated with fetal megacystis.MethodsThis was a retrospective multicenter study of cases referred to the fetal medicine unit of one of the eight academic hospitals in The Netherlands with a diagnosis of fetal megacystis. For each case, data on and measurements of fetal urinary tract and associated structural anomalies were collected. All available postmortem examinations and postnatal investigations were reviewed in order to establish the final diagnosis. In the first trimester, fetal megacystis was defined as longitudinal bladder diameter (LBD) ≥ 7 mm, and in the second and third trimesters as an enlarged bladder failing to empty during an extended ultrasound examination lasting at least 40 min.ResultsOf the 541 pregnancies with fetal megacystis, it was isolated (or solely accompanied by other signs of lower urinary tract obstruction (LUTO)) in 360 (67%) cases and associated with other abnormal ultrasound findings in 181 (33%) cases. The most common associated ultrasound anomaly was an increased nuchal translucency thickness (22%), followed by single umbilical artery (10%) and cardiac defect (10%). A final diagnosis was established in 418 cases, including 222 (53%) cases with isolated LUTO and 60 (14%) infants with normal micturition or minor isolated urological anomalies. In the remaining 136 (33%) cases, concomitant developmental or chromosomal abnormality or genetic syndrome was diagnosed. Overall, 40 chromosomal abnormalities were diagnosed, including trisomy 18 (n = 24), trisomy 21 (n = 5), Turner syndrome (n = 5), trisomy 13 (n = 3) and 22q11 deletion (n = 3). Thirty‐two cases presented with anorectal malformations involving the anus, rectum and urogenital tract. In cases with confirmed urethral and anal atresia, megacystis occurred early in pregnancy and the bladder appeared severely distended (the LBD (in mm) was equal to or greater than twice the gestational age (in weeks)). Fetal macrosomia was detected in six cases and an overgrowth syndrome was detected in four cases, comprising two infants with Beckwith–Wiedemann syndrome and two with Sotos syndrome. Megacystis‐microcolon‐intestinal hypoperistalsis syndrome was diagnosed in five (1%) cases and prenatally suspected only in one case.ConclusionsAlthough the main cause of fetal megacystis is LUTO, an enlarged fetal bladder can also be present as a concomitant finding of miscellaneous genetic syndromes, developmental disturbances and chromosomal abnormalities. We provide an overview of the structural anomalies and congenital disorders associated with fetal megacystis and propose a practical guide for the differential diagnosis of genetic syndromes and chromosomal and developmental abnormalities in pregnancies presenting with fetal megacystis, focusing on the morphological examination of the fetus. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Semen and male genital tract characteristics of patients with Fabry disease: the FERTIFABRY multicentre observational study

BackgroundFabry disease (FD) is a rare disorder caused by the deficient activity of α-galactosidase A (α-Gal A). This enzymatic deficit results in the cellular accumulation of globotriaosylceramide (GL-3 or Gb3) and related glycosphingolipids in practically all organs and tissues in the body. The identification of deposits of Gb3 at the reproductive tract level suggests that this part of the body might be involved. We undertook this study to assess the impact of Fabry disease in male gonadal function.Materials and methodsThis was a multicentre cross-sectional, prospective study that included patients aged 18 to 65 years with Fabry disease, receiving care in a specialized institution. The prevalence of at least one abnormal category in the semen analysis was presented with 95% confidence intervals (CI). The association between infertility and semen analysis abnormality was assessed by Fisher’s exact test. The association of factors associated with fertility or semen analysis abnormality were analysed by a multivariable logistic regression model and expressed by an odds ratio (OR) and its bilateral 95% CI.ResultsOverall, 14 (82.4% [95% CI, 56.6–96.2]) of the patients had at least one abnormal category in the semen analysis based on WHO criteria. Sixteen patients responded to the questionnaire on fertility, 11 of whom were classified as fertile. Nine of the 11 fertile patients presented at least one abnormal category in the semen analysis. No association was found between infertility and semen analysis abnormality (p = 1.0000). Age of patient at inclusion (OR, 1.19; 95% CI, 0.98 to 1.45; p = 0.0854) and duration of replacement therapy (OR, 1.28; 95% CI, 0.96 to 1.65; p = 0.1263) were associated with sperm abnormalities. Eleven of the 16 patients had a normal hormonal profile. An ultrasound anomaly of the genital tract was observed in 12 patients.ConclusionsThese results suggest that, while FD might have a detrimental effect on the semen characteristics, the reproductive function diminished only slightly. Further studies are warranted to assess the impact of the disease and of sperm abnormalities in the fertility of male patients with FD.

Prenatal ultrasound findings of rasopathies in a cohort of 424 fetuses: update on genetic testing in the NGS era

BackgroundThis study evaluates 6 years of prenatal rasopathy testing in the Netherlands, updates on previous data and gives recommendations for prenatal rasopathy testing.Methods424 fetal samples, sent in for prenatal rasopathy...

Chromosomal microarray comparative genome hybridization (arrayCGH) in prenatal settings. Proposal for Hungarian application in clinical practice

Invasive prenatal testing and conventional G-banding chromosome analysis have been considered to be the gold standard of fetal cytogenetic diagnosis. Standard karyotyping is, however, constrained by the limits of the resolution of using a microscope. The advantage of molecular karyotyping, array based methods is the evaluation of sub-microscopic copy number changes across the whole genome in a single analysis. The application of array comparative genome hybridization has greatly increased the detection of pathogenic chromosomal abnormalities in prenatal settings. Based on available data in the international literature of the last decade, the clinical utility of arrayCGH is the recognition of some 1-2% and 5-7% additional genetical information compared to metaphase karyotype alone in fetuses without ultrasound anomaly and in fetuses with ultrasonographically detected malformations, respectively. Thus arrayCGH improves the prenatal diagnosis of genetic abnormalities mainly in fetuses with structural sonographic findings. In the present paper we review the literature of chromosomal microarray and make a proposal for the application of the method in Hungarian prenatal genetical practice. Orv Hetil. 2019; 160(13): 484-493.

Chromosomal Microarray Analysis versus Karyotyping in Fetuses with Increased Nuchal Translucency.

We have carried out a retrospective study of chromosome anomalies associated with increased nuchal translucency (NT) in order to compare yield rates of karyotype, chromosome microarray analysis (CMA), and non-invasive prenatal testing (NIPT) in this condition. Presenting with increased NT or cystic hygroma ≥3.5 mm as an isolated sign, 249 fetuses underwent karyotype and/or CMA from 11 to 18 gestational weeks. Karyotype and fluorescence in situ hybridization (FISH) analyses detected 103 chromosomal anomalies including 95 aneuploidies and eight chromosomal rearrangements or derivatives. Further, seven pathogenic copy number variants (CNV), five likely pathogenic CNVs, and 15 variants of unknown significance (VOUS) were detected by CMA in fetuses with normal karyotype. Genetic testing is now facing new challenges due to results with uncertain clinical impacts. Additional investigations will be necessary to interpret these findings. More than 15% of the anomalies that we have diagnosed with invasive techniques could not be detected by NIPT. It is therefore definitely not recommended in the case of ultrasound anomalies. These results, while corroborating the use of CMA in fetuses with increased NT as a second tier after rapid aneuploidy testing, do not suggest a dismissal of karyotype analysis.