Search

Congenital heart defects (CHDs) appear in 8-10 out of 1000 live born newborns and are one of the most common causes of deaths. In fetuses, the congenital heart defects are found even 3-5 times more often. Currently, microarray comparative genomic hybridization (array CGH) is recommended by worldwide scientific organizations as a first-line test in the prenatal diagnosis of fetuses with sonographic abnormalities, especially cardiac defects. We present the results of the application of array CGH in 484 cases with prenatally diagnosed congenital heart diseases by fetal ultrasound scanning (256 isolated CHD and 228 CHD coexisting with other malformations). We identified pathogenic aberrations and likely pathogenic genetic loci for CHD in 165 fetuses and 9 copy number variants (CNVs) of unknown clinical significance. Prenatal array-CGH is a useful method allowing the identification of all unbalanced aberrations (number and structure) with a much higher resolution than the currently applied traditional assessment techniques karyotype. Due to this ability, we identified the etiology of heart defects in 37% of cases.

Purpose: To evaluate the trends in prenatal diagnosis over 26 years in a tertiary referral hospital., Methods: A retrospective analysis of invasive prenatal procedures performed between 1991 and 2016. Maternal characteristics, indications for invasive diagnosis, and percentage of abnormal karyotypes were compared between periods according to guidelines implemented nationally and locally., Results: A total of 14,302 invasive prenatal procedures were performed. The proportion of invasive procedures performed for advanced maternal age, abnormal karyotype in a previous pregnancy, and maternal anxiety decreased from 71.1%, 17.8%, 8.9% in 1991 to 23.9%, 1.3%, and 2.3% in 2016 (OR 0.6, 0.8, and 0.9 for each 5 years, respectively; p < 0.001), while the proportion of invasive procedures performed for abnormal ultrasound increased from 2.2% in 1991 to 51.6% in 2016 (OR 1.9 for each 5 years; p < 0.001). Abnormal karyotype was found in 9.7%. The proportion of abnormal karyotypes increased significantly from 0.0% in 1991 to 15.7% in 2016 (OR 1.35 for each 5-year period; p < 0.001). The odds of abnormal karyotype increased after the implementation of the Ordinance of the Minister of Health in 2003 (OR 1.6), the National Prenatal Screening Program in 2007 (OR 2.2), and the in-house genetic counseling with combined first trimester screening in 2015 (OR 3.1)., Conclusions: Significant changes in prenatal diagnosis led to a better selection of patients undergoing invasive prenatal procedures. The implementation of in-house genetic counseling was associated with an increased rate of the detection of abnormal karyotypes.

Objective: To present five new cases of prenatally diagnosed Pallister-Killian syndrome (PKS) and to propose an approach for a targeted diagnosis., Method: We retrospectively analyzed ultrasound findings and cytogenetic results in PKS. We also searched through dysmorphology databases for features occurring in PKS that could potentially be seen in prenatal ultrasound examination., Results: On the basis of collected data, frequent and distinctive features in fetuses with PKS were established. The most appropriate material and method of testing were proposed. Rhizomelic limb shortening, diaphragmatic hernia, thickened nuchal fold, increased prenasal thickness, polydactyly and polyhydramnios were frequent and distinctive findings in fetuses with PKS. Amniocentesis was the most frequent prenatal procedure for material collection. Percentage of aneuploid cells was higher in amniotic fluid than in cord blood. Cytomolecular tests were useful as confirmation as well as preliminary tests. Cytogenetic identification of the isochromosome was done in all cases except one., Conclusions: In case of ultrasound evaluation of features frequent and distinctive for PKS in second and third trimesters of pregnancy, targeted diagnosis should be considered. Amniotic fluid instead of cord blood collection is preferable. Communication with the laboratory is important because modification of routine procedures enhances a chance for correct diagnosis. © 2017 John Wiley & Sons, Ltd., (© 2017 John Wiley & Sons, Ltd.)

Craniosynostosis (a premature fusion of the cranial sutures) occurs with a frequency of 1 in 2100-2500 births and in over 40% cases is caused by known genetic factors--either single gene mutations or chromosomal rearrangements. Cases caused by complex chromosomal abnormalities are uncommon and likely associated with compound phenotype. Saethre-Chotzen syndrome (SCS) [#101400] is caused by TWIST1 gene haploinsufficiency. Its phenotype includes uni- or bicoronal synostosis, short stature, facial dysmorphism and variable anomalies of the hands and feet. Due to its poor sonographic manifestation a prenatal diagnosis of SCS is challenging. We report a case of a prenatally detected craniosynostosis (compound Saethre-Chotzen syndrome phenotype) caused by a de novo complex chromosomal rearrangement (1; 4; 7) with a microdeletion of 7p21.3-7p15.3, including TWIST1 gene.

Objectives: The aim of the study was to present initial results of non-invasive prenatal diagnosis of common aneuploidies of chromosomes 21, 18 and 13 based on cell-free fetal DNA in maternal serum in high-risk patients, and to compare the results with routine karyotyping., Material and Methods: Before the invasive procedure, 10 ml of peripheral blood from 10 patients was collected to isolate cell-free fetal DNA and to perform a non-invasive fetal trisomy test (NIFTY provided by Beijing Genomics Institute, BGI, Shenzen, China)., Results: Three out of 10 samples showed an abnormal karyotype in traditional karyotyping. There were 9 conclusive NIFTY results. NIFTY detected 1 out of 2 trisomies 18. The quantity of cell-free fetal DNA in maternal plasma in the second probe with trisomy 18 was unsatisfactory fora conclusive NIFTY result. In 1 case traditional karyotyping revealed mosaicism impossible to detect with NIFTY

Objectives: The aim of our study was to determine the risk of aneuploidy and associated malformations in fetuses with holoprosencephaly. We have also analyzed the gestational age during the first examination., Design: We have studied ultrasound reports of fetuses with holoprosencephaly., Materials and Methods: We analyzed 33 cases, diagnosed in the course of the last eight years in our center. All fetuses underwent a detailed ultrasound survey and, in most cases, antenatal karyotyping. In all cases the type of holoprosencephaly was assessed., Results: In analyzed fetuses alobar holoprosencephaly was diagnosed in 24, semilobar in 7 and lobar holoprosencephaly in 2 cases. Associated anomalies were detected in 28 (mostly face defects) and chromosomal abnormalities in 12 cases. The median gestational age at the first examination was 25 weeks. No more than 14 examinations had been performed before 24 week., Conclusions: Our findings suggest that in case of fetuses with holoprosencephaly, a detailed ultrasound survey and karyotyping are essential to be performed in all cases. For that reason, patients with fetuses with holoprosencephaly should be diagnosed as early as possible in the referral center.

Objectives: Our objective was to determine if ventriculomegaly not related to the open neural tube defects is associated with other anomalies and aneuploidy. What we should do after such diagnosis. We also analyzed gestational age at the first examination., Design: We retrospectively studied ultrasound reports of the fetuses with this type of ventriculomegaly., Materials and Methods: We analyzed 71 cases diagnosed between September 1997 and March 2002. Ventriculomegaly was a assumed to be present when atrial width was equal or greater than 10 mm. Antenatal karyotyping was performed in all fetuses., Results: 21 cases were concomitant with other CNS malformations, in 50 cases ventriculomegaly was the only one brain anomaly. The incidence of chromosomal abnormalities was 8.5% and it was strongly related to the presence of multisystem malformations. The median gestational age at diagnosis was 27.6 weeks., Conclusions: Our results suggest that in fetuses with ventriculomegaly not related to the open neural tube defects a detailed ultrasonographic survey and karyotyping should be done. Furthermore, every pregnant woman should undergo ultrasound screening before the 24th gestational week.

Objectives: To analyse additional structural and genetic anomalies in fetuses with acrania/exencephaly/anencephaly sequence (AEAS). Methods: A retrospective analysis of 139 fetuses with AEAS diagnosed between 2006 and 2020 in a single tertiary referral ultrasound department. Results: The median gestational age at diagnosis decreased from 15 weeks in 2006 to 13 weeks in 2020 (− 0.21 per each year; p = 0.009). In 103 fetuses, the defects were limited to the neural tube (NTD) (74.1%), in 36 fetuses (25.9%), there were additional structural non-NTD anomalies. The most common were ventral body wall defects present in 17.8% (23/139), followed by anomalies of the limbs (7.2%; 10/139), face (6.5%; 9/139) and heart (6.5%; 9/139). Genetic anomalies were diagnosed in 7 of the 74 conclusive results (9.5%; 7/74; trisomy 18, n = 5; triploidy, n = 1; duplication of Xq, n = 1). In univariate logistic regression models, male sex, limb anomalies and ventral body wall defects significantly increased the risk of genetic anomalies (OR 12.3; p = 0.024; OR 16.5; p = 0.002 and OR 10.4; p = 0.009, respectively). Conclusions: A significant number of fetuses with AEAS have additional structural non-NTD anomalies, which are mostly consistent with limb body wall complex. Genetic abnormalities are diagnosed in almost 10% of affected fetuses and trisomy 18 is the most common aberration. Factors that significantly increased the odds of genetic anomalies in fetuses with AEAS comprise male sex, limb anomalies and ventral body wall defects. [ABSTRACT FROM AUTHOR]

We present three new cases and review of the literature on the prenatal diagnosis of Emanuel syndrome (ES). Twenty-one foetuses have been analysed. In all three cases diagnosed in our department, posterior fossa abnormalities were seen and in one hypoplastic right ventricle was diagnosed at the first trimester scan. Defects of the posterior fossa (62% of foetuses; 13/21) and left diaphragmatic hernia (29% of foetuses; 6/21) are the most frequently reported prenatal findings in ES syndrome. No pattern of specific prenatal ultrasound markers of ES exists. Abnormalities of the posterior fossa are frequent and may be diagnosed as early as in the first trimester of pregnancy. Specific diagnosis can be made only after invasive genetic testing. What is already known on this subject? Emanuel syndrome (ES) is a rare genetic disorder. No pattern of specific prenatal ultrasound markers exists. The great majority of cases is diagnosed postnatally and only a few cases of prenatal diagnosis have been published to date. What do the results of this study add? The most frequent structural abnormalities in prenatally detected ES involved central nervous system (80.9%), namely posterior fossa defects (57.1%) and mild ventriculomegaly (23.8%). Other frequent abnormalities include left diaphragmatic hernia (28.6%), renal defects (23.8%) and foetal growth restriction (FGR) (23.8%). What are the implications of these findings for clinical practice and/or further research? Abnormalities of the posterior fossa are the most frequent defects in ES and may be diagnosed as early as in the first trimester of pregnancy. Specific diagnosis can be made only after invasive genetic testing. [ABSTRACT FROM AUTHOR]

Background: Despite advances in routine prenatal cytogenetic testing, most anomalous fetuses remain without a genetic diagnosis. Exome sequencing (ES) is a molecular technique that identifies sequence variants across protein-coding regions and is now increasingly used in clinical practice. Fetal phenotypes differ from postnatal and, therefore, prenatal ES interpretation requires a large amount of data deriving from prenatal testing. The aim of our study was to present initial results of the implementation of ES to prenatal diagnosis in Polish patients and to discuss its possible clinical impact on genetic counseling. Methods: In this study we performed a retrospective review of all fetal samples referred to our laboratory for ES from cooperating centers between January 2017 and June 2021. Results: During the study period 122 fetuses were subjected to ES at our institution. There were 52 abnormal ES results: 31 in the group of fetuses with a single organ system anomaly and 21 in the group of fetuses with multisystem anomalies. The difference between groups was not statistically significant. There were 57 different pathogenic or likely pathogenic variants reported in 33 different genes. The most common were missense variants. In 17 cases the molecular diagnosis had an actual clinical impact on subsequent pregnancies or other family members. Conclusions: Exome sequencing increases the detection rate in fetuses with structural anomalies and improves genetic counseling for both the affected couple and their relatives. [ABSTRACT FROM AUTHOR]

Background: Non-invasive prenatal testing (NIPT) is a rapidly developing and widely used method in the prenatal screening. Recently, the widespread use of the NIPT caused a neglecting of the limitations of this technology. Case presentation: The 38-year-old woman underwent amniocentesis because of a high risk of trisomy 2 revealed by the genome-wide Non-Invasive Prenatal Test (NIPT). The invasive prenatal diagnosis revealed the mosaicism for a small supernumerary marker chromosome sSMC derived from chromosome 2. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed three signals of centromere 2 in 30% of the cells. GTG-banded metaphases revealed abnormal karyotype (47,XX,+mar[21]/46,XX[19]) and was confirmed by array comparative genomic hybridization (aCGH). Cytogenetic analyses (FISH, aCGH, karyotype) on fetal skin biopsies were performed and confirmed the genomic gain of the centromeric region of chromosome 2. In the placenta, three cell lines were detected: a normal cell line, a cell line with trisomy 2 and a third one with only the sSMC. Conclusion: Whole-genome Non-Invasive Prenatal Testing allows not only the identification of common fetal trisomies but also diagnosis of rare chromosomal abnormalities. Especially in such cases, it is extremely important to perform not only NIPT verification on a sample of material other than trophoblast, but also to apply appropriate research methods. Such conduct allows detailed analysis of the detected aberration, thus appropriate clinical validity. [ABSTRACT FROM AUTHOR]