-
Archives of Gynecology and Obstetrics Apr 2023A systematic evaluation of the fetal anatomy as part of the second trimester ultrasound examination in pregnancy is useful in detecting pregnancy complications, fetal... (Review)
Review
A systematic evaluation of the fetal anatomy as part of the second trimester ultrasound examination in pregnancy is useful in detecting pregnancy complications, fetal abnormalities, and genetic diseases. We aim to illustrate the basic and detailed second trimester scan, according to current international and national guidelines, as well as to our own every-day practice in the Department for Prenatal Diagnosis at the University of Tübingen, Germany.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, Second; Ultrasonography, Prenatal; Fetus; Prenatal Diagnosis; Prenatal Care; Pregnancy Trimester, First
PubMed: 35543741
DOI: 10.1007/s00404-022-06569-2 -
Ultrasound in Obstetrics & Gynecology :... Apr 2023Congenital pulmonary artery anomalies are rare. Their antenatal diagnosis requires good knowledge of fetal cardiac anatomy because their clinical presentation varies... (Review)
Review
Congenital pulmonary artery anomalies are rare. Their antenatal diagnosis requires good knowledge of fetal cardiac anatomy because their clinical presentation varies depending on the type and severity of the underlying lesion. Screening of these vascular anomalies can be straightforward in some cases because of significant associated consequences that are detected easily on ultrasound, while other anomalies have considerably less obvious features. There may be an associated genetic syndrome. The aim of this review was to define anomalies of the main pulmonary artery and its branches and to propose, through the identification of suspicious findings during routine antenatal heart examination, an optimal screening method for the pulmonary artery pathway. We propose that pulmonary artery anomalies can be classified antenatally into four types of disorder. Herein we describe 14 cases subgrouped accordingly as: anomalies of the pulmonary valvular region, with stenosis or atresia of the valve (n = 4); conotruncal abnormalities (n = 4); anomalies associated with abnormal origin or course of the pulmonary artery (n = 4); and anomalies associated with abnormal growth of the pulmonary artery and its branches (n = 2). We highlight the need to differentiate the three-vessel view from the three-vessel-and-trachea view when assessing a fetus with a congenital pulmonary artery anomaly. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Female; Humans; Pulmonary Artery; Ultrasonography, Prenatal; Prenatal Diagnosis; Heart Defects, Congenital; Fetus; Vascular Malformations
PubMed: 36178851
DOI: 10.1002/uog.26078 -
Prenatal Diagnosis Dec 2022Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. Historically, diagnosis was primarily... (Review)
Review
OBJECTIVE
Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. Historically, diagnosis was primarily via postnatal imaging. Our objective was to establish the prenatal phenotype/genotype correlations of tubulinopathies identified by fetal imaging.
METHODS
A large, multicenter retrospective case series was performed across nine institutions in the Fetal Sequencing Consortium. Demographics, fetal imaging reports, genetic screening and diagnostic testing results, delivery reports, and neonatal imaging reports were extracted for pregnancies with a confirmed molecular diagnosis of a tubulinopathy.
RESULTS
Nineteen pregnancies with a fetal tubulinopathy were identified. The most common prenatal imaging findings were cerebral ventriculomegaly (15/19), cerebellar hypoplasia (13/19), absence of the cavum septum pellucidum (6/19), abnormalities of the corpus callosum (6/19), and microcephaly (3/19). Fetal MRI identified additional central nervous system features that were not appreciated on neurosonogram in eight cases. Single gene variants were reported in TUBA1A (13), TUBB (1), TUBB2A (1), TUBB2B (2), and TUBB3 (2).
CONCLUSION
The presence of ventriculomegaly with cerebellar abnormalities in conjunction with additional prenatal neurosonographic findings warrants additional evaluation for a tubulinopathy. Conclusive diagnosis can be achieved by molecular sequencing, which may assist in coordination, prognostication, and reproductive planning.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Nervous System Malformations; Fetus; Microcephaly; Prenatal Diagnosis; Magnetic Resonance Imaging; Hydrocephalus; Ultrasonography, Prenatal; Multicenter Studies as Topic
PubMed: 36403095
DOI: 10.1002/pd.6269 -
Archives of Gynecology and Obstetrics Mar 2022
Topics: Amniocentesis; COVID-19; Female; Humans; Pandemics; Pregnancy; Prenatal Diagnosis; SARS-CoV-2
PubMed: 34618213
DOI: 10.1007/s00404-021-06276-4 -
Ultrasound in Obstetrics & Gynecology :... Jun 2023To report on a large cohort of fetuses with mild forms of tubulinopathy and to define prenatal ultrasound and magnetic resonance imaging (MRI) features that can...
OBJECTIVE
To report on a large cohort of fetuses with mild forms of tubulinopathy and to define prenatal ultrasound and magnetic resonance imaging (MRI) features that can facilitate prenatal diagnosis.
METHODS
This was a retrospective multicenter study of fetuses diagnosed between January 2007 and February 2022 with a mild tubulinopathy (without lissencephaly or microlissencephaly). We collected and reviewed brain imaging and genetic data, and defined major criteria as findings observed in ≥ 70% of the patients and minor criteria as those observed in ≥ 50% but < 70% of the patients.
RESULTS
Our cohort included 34 fetuses. The mean gestational age at ultrasound screening, when suspicion of a central nervous system anomaly was first raised, was 24.2 (range, 17-33) weeks. Callosal anomalies (n = 19 (56%)) and abnormal ventricles (n = 18 (53%)) were the main reasons for referral. The mean gestational age at neurosonography was 28.3 (range, 23-34) weeks and that at MRI was 30.2 (range, 24-35) weeks. Major ultrasound criteria were midline distortion, ventricular asymmetry, dysmorphic and/or dilated frontal horn(s) and abnormal sulcation. Minor ultrasound criteria were distortion of the cavum septi pellucidi, abnormal corpus callosum, absent or asymmetric olfactory sulci, ventriculomegaly and basal ganglia dysmorphism. Major MRI criteria were midline distortion, distortion of the cavum septi pellucidi, ventricular asymmetry, dilatation (generally unilateral) and/or distortion, dysmorphic and/or dilated frontal horn(s) and abnormal sulcation (mainly dysgyria). Minor MRI criteria were absent or asymmetric olfactory sulci, abnormal bulge of the pons, anteroposterior diameter of the pons ≤ 5 centile and brainstem asymmetry. A mutation was found in TUBB3 (44.1% of cases), TUBB (23.5%), TUBB2B (14.7%) or TUBA1A (17.6%). The mutation was inherited from a parent in 18/34 cases. The pregnancy was terminated in 23/34 cases.
CONCLUSIONS
Prenatal diagnosis of mild forms of tubulinopathy is possible but challenging. We have defined, in this large series of fetuses, major and minor criteria that can help identify this entity in utero. Most findings can be visualized on ultrasound. This evaluation is also important for prenatal counseling. Once a prenatal diagnosis of mild tubulinopathy is suspected, the family members should be referred for exome sequencing and MRI. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Female; Humans; Infant; Ultrasonography, Prenatal; Nervous System Malformations; Brain; Prenatal Diagnosis; Fetus; Gestational Age; Retrospective Studies; Magnetic Resonance Imaging
PubMed: 36484554
DOI: 10.1002/uog.26140 -
Prenatal Diagnosis May 2022DNA sequencing technologies for clinical genetic testing have been rapidly evolving in recent years, and steadily become more important within the field of prenatal... (Review)
Review
DNA sequencing technologies for clinical genetic testing have been rapidly evolving in recent years, and steadily become more important within the field of prenatal diagnostics. This review aims to give an overview of recent developments and to describe how they have the potential to fill the gaps of the currently clinically implemented methods for prenatal diagnosis of various genetic disorders. It has been shown for postnatal testing that whole genome sequencing provides a set of added benefits compared to exome sequencing, and it is to be expected that this will be the case for prenatal testing as well. RNA-sequencing, already used postnatally, can provide valuable complementary data to DNA-based testing, and aid in variant interpretation. While not ready for clinical implementation, emerging technologies such as long-read and Hi-C sequencing analyses might add to the toolbox for interpreting the expanding genetic data sets generated by genome-wide sequencing. Lastly, we also discuss some more practical implications of introducing these emerging technologies, which generate larger and larger genomic data sets, in the prenatal field.
Topics: Female; Genetic Testing; Humans; Pregnancy; Prenatal Diagnosis; Sequence Analysis, DNA; Sequence Analysis, RNA; Exome Sequencing
PubMed: 35416301
DOI: 10.1002/pd.6146 -
Ultrasound in Obstetrics & Gynecology :... Mar 2022
Topics: Female; Hemangioma; Humans; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal; Umbilical Cord
PubMed: 34435409
DOI: 10.1002/uog.24755 -
Ultraschall in Der Medizin (Stuttgart,... Jun 2023Diagnostic puncture (amniocentesis, chorionic villus sampling, and fetal blood sampling) is an essential part of prenatal diagnostics and the only established and... (Review)
Review
Diagnostic puncture (amniocentesis, chorionic villus sampling, and fetal blood sampling) is an essential part of prenatal diagnostics and the only established and sufficiently scientifically evaluated possibility of diagnosing genetic diseases from pregnancy-specific cells. The number of diagnostic punctures in Germany, as in other countries, has fallen significantly. This is largely due to the introduction of first-trimester screening with further detailed ultrasound examination of the fetus and the analysis of cf-DNA (cell-free DNA) from maternal blood (noninvasive prenatal test - NIPT). On the other hand, knowledge about the incidence and appearance of genetic diseases has increased. The development of modern molecular genetic techniques (microarray and exome analysis) makes a differentiated investigation of these diseases increasingly possible. The requirements for education and counseling regarding these complex correlations have thus increased. The studies performed in recent years make it clear that diagnostic puncture performed in expert centers is associated with a low risk of complications. In particular, the procedure-related miscarriage risk hardly differs from the background risk for spontaneous abortion. In 2013, the Section of Gynecology and Obstetrics of the German Society for Ultrasound in Medicine (DEGUM) published recommendations on diagnostic puncture in prenatal medicine 1. The developments described above and new findings in recent years make it necessary to revise and reformulate these recommendations. The aim of this review is to compile important and current facts regarding prenatal medical puncture (including technique, complications, genetic examinations). It is intended to provide basic, comprehensive, and up-to-date information on diagnostic puncture in prenatal medicine. It replaces the publication from 2013 1.
Topics: Pregnancy; Female; Humans; Prenatal Diagnosis; Amniocentesis; Chorionic Villi Sampling; Pregnancy Trimester, First; Genetic Testing
PubMed: 36882109
DOI: 10.1055/a-2014-4505 -
BMC Medical Genomics Oct 2023Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of...
BACKGROUND
Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of prenatal WES and to investigate the pathogenic variants in structurally abnormal fetuses.
METHODS
We recruited 144 fetuses with structural anomalies between 14 and 2020 and 15 December 2021 in the study. Genetic screening was performed by WES combined with karyotyping and chromosomal microarray analysis. The molecular diagnostic yield of prenatal WES for each type of fetal structural anomaly and the identified pathogenic genes and mutations were reported.
RESULTS
In this study, we retrospectively analyzed the clinical and genetic data of 145 structurally anomalous fetuses. These cases were classified into 9 phenotypic classes based on antenatal ultrasound findings. Thirty-eight pathogenic variants in 24 genes were identified in 35 of the 145 cases, including 14 novel variants in 13 genes (EP300, MYH3, TSC2, MMP9, CPLANE1, INVS, COL1A1, EYA1, TTC21B, MKS1, COL11A2, PDHA1 and L1CAM). Five additional pathogenic variants were classified as incidental findings. Our study showed that the overall diagnosis rate of WES was 28.1% (27/96) in the parent-fetus trio cases and 16.3% (8/49) in the proband-only cases. Fetuses with musculoskeletal anomalies had the highest diagnostic yield (51.4%, 19/37). In addition, FGFR3 and COL1A1 were the most common pathogenic genes.
CONCLUSIONS
Our work expands the mutation spectrum of the genes associated with fetal structural anomalies and provides valuable information for future parental genetic counselling and pregnancy management of the structurally anomalous fetuses.
Topics: Female; Humans; Pregnancy; East Asian People; Exome Sequencing; Fetus; Pregnancy Trimester, First; Prenatal Diagnosis; Retrospective Studies; Ultrasonography, Prenatal; Congenital Abnormalities
PubMed: 37880672
DOI: 10.1186/s12920-023-01697-3 -
Pediatric Radiology Sep 2023Congenital thoracic anomalies are uncommon malformations that require a precise diagnosis to guide parental counseling and possible prenatal treatment. Prenatal...
Congenital thoracic anomalies are uncommon malformations that require a precise diagnosis to guide parental counseling and possible prenatal treatment. Prenatal ultrasound (US) is the gold standard imaging modality to first detect and characterize these abnormalities and the best modality for follow-up. Fetal magnetic resonance imaging (MRI) is a complementary tool that provides multiplanar assessment and tissue characterization and can help estimate prognosis. Prenatal treatment is increasingly being used in fetuses with signs of distress and to potentially decrease morbidity and mortality. In this essay, the authors illustrate side-by-side US, MRI and therapeutic options for congenital thoracic anomalies in cases that presented to a tertiary pediatric hospital during the 7-year period 2014-2021. Entities included are congenital diaphragmatic hernia, congenital pulmonary airway malformation, bronchopulmonary sequestration, hybrid lesions, foregut duplications cysts and congenital lobar overinflation. Treatment options include maternal steroids, thoraco-amniotic shunt and fetal endotracheal occlusion. Recognition of typical findings in congenital thoracic anomalies is helpful to establish diagnosis, predict prognosis and plan perinatal treatment.
Topics: Pregnancy; Female; Humans; Child; Prenatal Diagnosis; Hernias, Diaphragmatic, Congenital; Magnetic Resonance Imaging; Cystic Adenomatoid Malformation of Lung, Congenital; Ultrasonography, Prenatal
PubMed: 37166455
DOI: 10.1007/s00247-023-05681-y