Prenatal Findings Research Articles

VP11.10: Prenatal findings and follow‐up of a fetus with cloacal exstrophy

VP11.10: Prenatal findings and follow‐up of a fetus with cloacal exstrophy

VP11.13: Prenatal findings, management and prognosis of a Meckel diverticulum case

VP11.13: Prenatal findings, management and prognosis of a Meckel diverticulum case

Fetal ciliopathies: a retrospective observational single-center study

PurposeReport on the diagnosis of prenatally suspected multisystem ciliopathies in a single center between 2002 and 2020.MethodsRetrospective observational single-center study including pregnancies with prenatal ultrasound features of multisystem ciliopathies, such as hyperechogenic kidneys together with polydactyly and/or other skeletal and extraskeletal findings. Cases were compared according to their prenatal findings and outcomes.Results36 cases of multisystem ciliopathies were diagnosed. Meckel-Gruber syndrome (MKS) was the most common ciliopathy (n = 19/36, 52.8%), followed by disorders that belong to the group of short-rib thoracic dysplasia (SRTD, n = 10/36, 27.8%) McKusick–Kaufmann syndrome (MKKS, n = 4/36, 11.1%), Bardet–Biedl syndrome (BBS, n = 2/36, 5.5%) and Joubert syndrome (n = 1/36, 2.8%). All cases showed abnormalities of the kidneys, most often hyperechogenic parenchyma (n = 26/36, 72.2%), cystic dysplasia (n = 24/36, 66.7%), and/or bilateral kidney enlargement (n = 22/36, 61.1%). Oligohydramnios was mainly present in fetuses with MKS. Polydactyly (n = 18/36), abnormalities of the CNS (n = 25/36), and heart defects (n = 10/36) were associated in 50%, 69.4%, and 27.8%, respectively.ConclusionPrenatal detection of renal abnormalities associated with skeletal or brain abnormalities should raise the suspicion for multisystem ciliopathies. Prenatal ultrasound can help to differentiate between different diseases and pave the way for subsequent targeted genetic testing.

VP27.01: Fetal isolated ventriculomegaly: prenatal findings and long‐term follow up

VP27.01: Fetal isolated ventriculomegaly: prenatal findings and long‐term follow up

VP13.10: Prenatal findings in a fetus presenting pulmonary stenosis, polyhydramnios, nuchal fold and bell‐shaped thorax with coat‐hanger sign

VP13.10: Prenatal findings in a fetus presenting pulmonary stenosis, polyhydramnios, nuchal fold and bell‐shaped thorax with coat‐hanger sign

VP29.04: Prenatal diagnosis of Leigh disease caused due to novel mutation in ISCA2 gene in nuclear DNA

Leigh disease/subacute necrotising encephalopathy also known as the multiple mitochondrial dysfunctions syndrome (MMDS) type 4 is a Mitochondrial disease which can be caused by mutations of nuclear or mitochondrial DNA. Leigh disease is inherited in an autosomal recessive manner and each pregnancy will carry the 25% risk of the fetus to be affected with it. Diagnosis of most of the cases of Leigh's disease is postnatal and retrospective as the disease manifests between the ages of 2 to 7 months of life with a triad of neurodevelopmental regression, optic atrophy with nystagmus, and diffuse white matter disease. To date, there is no cure for affected patients, and treatment options are mostly unsatisfactory. Prenatal ultrasound findings and immediate postnatal course of cases affected with Leigh Disease are unremarkable in most of the cases. Herewith we describe a prenatal molecular diagnosis of Leigh disease caused by ISCA2 (Iron-Sulphur cluster assembly 2) gene mutation - c.174G > A (p.Gln58(=)). Prenatal diagnosis was sought after establishing the genetic basis of Leigh disease in the previously affected index child having typical symptoms of the disease. Both parents were also identified as heterozygous carriers of same ISCA2 gene mutation. High degree of suspicion is required to achieve prenatal diagnosis of Leigh disease which can be easily missed prenatally. To the best of our knowledge, this is the first case report of Prenatal diagnosis of Leigh disease caused due to novel mutation in ISCA2 gene. Achieving prenatal diagnosis of Leigh syndrome helped parents to make well informed decision about continuation/termination of pregnancy as the disease will cause tremendous socio-economic and emotional burden to them. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

VP16.14: Diagnosis of short rib polydactyly syndrome type IV (Beemer‐Langer syndrome): a case report

Short rib-polydactyly syndrome (SRPS) is a rare congenital autosomal recessive inherited disease classified in four subtypes. Prenatal ultrasonography findings and postnatal examinations may help classify in one of four subtypes. We present a case of an infant who presented multiple congenital anomalies and the postnatal radiography helped to classify the SRPS as type IV (Beemer-Langer). A 23-year-old was referred for prenatal ultrasound which showed cystic hygroma, small omphalocele and choledocal cyst. Chromosomal analysis revealed a normal male karyotype. Morphological scan revealed small thorax, short ribs, micromelic shortening of limbs with the tibia slightly longer than the fibula, unilateral clubfoot, hidrocephalus and renal hiperechogenicity. Magnetic Resonance performed at 35 weeks revealed micrognathia and mesenteric lymphangioma. The infant delivered at 38 weeks of gestation and died within 60 minutes due to respiratory failure. Postmortem radiography showed marked shortening of all long bones, strikingly narrow thorax with short and horizontal ribs, highly placed clavicles, small scapulae, small ilia and the tibia was longer then the fibula. Identification of the SRPS subtype can be difficult due to overlap of clinical and pathologic findings. This case may help understanding Beemer-Langer type's phenotypic features such as micrognathia, cleft lip, hydrops, hydrocephalus and omphalocele. The most common radiological findings include narrow thorax with short ribs, short tubular bones, highly placed clavicle, small scapulae and ilia and bowing of radius and ulna with the tibia being longer than the fibula. The prognosis of Beemer-Langer syndrome is poor as infants usually die shortly after birth because of respiratory failure secondary to marked pulmonary hypoplasia.

Reply

We thank Drs Jing and Li for their thoughtful comments on our study1 and their reflections on prenatal screening for 22q11.2 deletion. They raise important points on which we would like to comment further and provide clarification. Drs Jing and Li suggest that ultrasound is more sensitive than cell-free DNA (cfDNA) testing in screening for 22q11.2 deletion, citing a study by Schindewolf et al.2. However, that study was intended to document the ultrasound findings seen most frequently in pregnancies with a 22q11.2 deletion in the second and third trimesters, not to determine the sensitivity of ultrasound for fetal 22q11.2 deletion. To our knowledge, this has not been evaluated in any study. Nonetheless, we agree that prenatal ultrasound findings have been well described by Schindewolf et al. and others and suggest that cfDNA screening in the first trimester can complement, not replace, second-trimester ultrasound as a screening tool for 22q11.2 deletion. As Drs Jing and Li note, the collective prevalence of other fetal microduplications and microdeletions is not insignificant, even when ultrasound is normal, and there is broad consensus that chorionic villus sampling or amniocentesis with microarray analysis should be offered whenever evaluation of a pregnancy for submicroscopic genomic alterations is desired. Similar to Drs Jing and Li, we would also welcome a method for accurate, genome-wide non-invasive prenatal screening with demonstrated clinical utility for detecting chromosomal imbalances at a resolution comparable to that of microarray, but currently available technologies fall short of this goal. In a prospective head-to-head comparison of genome-wide cfDNA testing and chromosomal microarray testing in 198 pregnancies, Guseh and colleagues showed that expanded non-invasive genome-wide screening has a lower detection rate for clinically significant chromosomal abnormalities when compared with that of chromosomal microarray analysis, and that pathogenic subchromosomal imbalances (< 7 Mb) contribute substantially to the missed abnormalities3. A clinical trial from The Eunice Kennedy Shriver National Institute of Child Health and Human Development showed that > 50% of (likely) pathogenic subchromosomal imbalances identified by chromosomal microarray analysis in anatomically normal fetuses are < 5 Mb in size4. We would also like to clarify a minor point. The cfDNA test evaluated in our study is described as ‘targeted’ in order to differentiate it from ‘genome-wide’ cfDNA testing because of the different technological design of the two approaches. It is not a standalone test for 22q11.2 deletion, as might have been misinterpreted from the phrasing. The Harmony® test screens for trisomy 21, trisomy 18 and trisomy 13, with the option of screening for sex chromosome aneuploidy and/or 22q11.2 deletion from the same blood collection. In many respects, we agree with Drs Jing and Li and support an approach to prenatal screening in which the benefits of cfDNA testing, ultrasound and diagnostic testing are incorporated to guide pregnancy management and improve outcome in 22q11.2 deletion syndrome and other prenatally diagnosable conditions.

VP16.13: Prenatal findings of a fetus with the autosomal recessive form of omodysplasia

VP16.13: Prenatal findings of a fetus with the autosomal recessive form of omodysplasia

VP16.07: Prenatal feature prenatal findings of a case of Noonan syndrome and Noonan syndrome‐like disorders

VP16.07: Prenatal feature prenatal findings of a case of Noonan syndrome and Noonan syndrome‐like disorders

Prenatal imaging findings of unilateral hypoplasia of A1 segment of anterior cerebral artery

Prenatal imaging findings of unilateral hypoplasia of A1 segment of anterior cerebral artery

Neonatal Hyperbilirubinemia and Cholestasis.

Neonatal Hyperbilirubinemia and Cholestasis.

Term Newborn with Corneal Opacity.

Term Newborn with Corneal Opacity.

Prenatal diagnosis, associated findings and postnatal outcome of fetuses with truncus arteriosus communis (TAC).

To assess the spectrum of associated anomalies, the intrauterine course, postnatal outcome and management of fetuses with truncus arteriosus communis (TAC) METHODS: All cases of TAC diagnosed prenatally over a period of 8years were retrospectively collected in two tertiary referral centers. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. 39 cases of TAC were diagnosed prenatally. Mean gestational age at first diagnosis was 22weeks (range, 13-38). Two cases were lost follow-up. Correct prenatal diagnosis of TAC was made in 21 of 24 (87.5%) cases and of TAC subtype in 19 of 21 (90.5%) cases. Prenatal diagnosis of TAC was incorrect in three cases: one newborn had aortic atresia with ventricular septal defect postnatally, one had hypoplastic right ventricle with dextro Transposition of the Great Arteries with coartation of the aorta and a third newborn had Tetralogy of Fallot with abnormal origin of the left pulmonary artery arising from the ascending aorta postnatally. These three cases were excluded from further analysis. In 9 of 34 (26.5%) cases, TAC was an isolated finding. 13 (38.2%) fetuses had additional chromosomal anomalies. Among them, microdeletion 22q11.2 was most common with a prevalence of 17.6% in our cohort. Another 3 fetuses were highly suspicious for non-chromosomal genetic syndromes due to their additional extra-cardiac anomalies, but molecular diagnosis could not be provided. Major cardiac and extra-cardiac anomalies occurred in 3 (8.8%) and in 20 (58.8%) cases, respectively. Predominantly, extra-cardiac anomalies occurred in association with chromosomal anomalies. Additionally, severe IUGR occurred in 6 (17.6%) cases. There were 14 terminations of pregnancy (41.2%), 1 (2.9%) intrauterine fetal death, 5 postnatal deaths (14.7%) and 14 (41.2%) infants were alive at last follow-up. Intention-to-treat survival rate was 70%. Mean follow-up among survivors was 42months (range, 6-104). Postoperative health status among survivors was excellent in 11 (78.6%) infants, but 5 (46.2%) of them needed repeated re-interventions due to recurrent pulmonary artery or conduit stenosis. The other 3 (21.4%) survivors were significantly impaired due to non-cardiac problems. TAC is a rare and complex cardiac anomaly that can be diagnosed prenatally with high precision. TAC is frequently associated with chromosomal and extra-cardiac anomalies, leading to a high intrauterine and postnatal loss rate due to terminations and perioperative mortality. Without severe extra-cardiac anomalies, postoperative short- and medium-term health status is excellent, independent of the subtype of TAC, but the prevalence of repeated interventions due to recurrent stenosis is high.

School-Age Outcome of Fetuses with Isolated Complete Septum Pellucidum Agenesis at Prenatal Magnetic Resonance Imaging.

To the best of our knowledge, there have not been studies to address the issue of long-term follow-up of patients with prenatal diagnosis of isolated complete septum pellucidum agenesis (SPA). The aim of this study was to acquire information about the school-age outcome of such patients as a resource for counseling parents receiving this prenatal finding. From a large fetal magnetic resonance (MR) database, we selected only those cases with isolated complete SPA as confirmed by two senior pediatric neuroradiologists in consensus; we then gathered information from the parents of those children who had reached the school age. None among the 12 cases (mean age at follow-up: 8.7 years, range: 6-13 year) of the resulting final cohort presented visual or stature deficits; only one required special teaching assistance in school. All other 11 children resulted without any notable academic issue. Our report may provide information of practical value about the school-age outcome of fetuses detected by prenatal MR imaging to carry isolated complete SPA.

Neurodevelopment and Genetic Evaluation of Sotos Syndrome Cases with a Novel Mutation: a Single-Center Experience.

Sotos syndrome is a non-progressive neurological disease with overgrowing, increased bone age, and developmental retardation. The aim of this study is to evaluate the prenatal, natal, and postnatal clinical findings of patients with Sotos syndrome. Sixteen patients suspected to have Sotos syndrome with clinical findings were examined retrospectively, ranging in ages between 3 and 23. In our file screening, we screened the FISH results of all 16 patients, but not all patients had NSD1 gene analysis results. We collected NSD1 gene analysis results, if there were any. The parameters that we investigated for these patients are birth weight, birth length, Apgar score at the 5th minute, dysmorphological face appearance, bone age, seizure, learning disability, feeding difficulties, surgical operation, and other accompanying abnormalities (brain MRI, abnormal echocardiographic findings, chronic otitis media, etc.). The anamnesis, clinical examination findings, and genetic reports of the patients were examined. For this, the hospital registration system was used. Breech presentation, Apgar score in the 5th minute of between 4 and 7, atrial septal defect at echocardiography, and consanguineous marriage rate were detected to be increased in individuals with Sotos syndrome compared to the normal population. When compared to the general population, delayed psychomotor development was determined. Macrocephaly, increased bone age, chronic otitis media frequency, and hernia operation frequency were determined to see if all patients were consistent with the literature. As a result of NSD1 gene sequencing analyses (NSD1 gene analysis was performed in 6 patients and a mutation was detected in 3 of them), three were found to have NSD1 gene mutation (one of them was novel). A novel deletion-type mutation that was not previously reported in the literature in the 19th exon of the NSD1 gene was determined. Xiphoidal protrusion was detected on this patient that had the novel mutation, and this situation has not been reported in the literature previously. If a patient has rapid growth, difficulty in learning, macrocephaly, speech delay, and timid personality, Sotos syndrome can be considered at the pre-diagnosis stage.

Overtreatment of Transient Maternal Hyperthyroidism Resulting in Fetal Goiter.

Overtreatment of Transient Maternal Hyperthyroidism Resulting in Fetal Goiter.

Predictive accuracy of prenatal ultrasound findings for lower urinary tract obstruction: A systematic review and Bayesian meta-analysis.

Lower urinary tract obstruction (LUTO) is a rare but critical fetal diagnosis. Different ultrasound markers have been reported with varying sensitivity and specificity. The objective of this systematic review and meta-analysis was to identify the diagnostic accuracy of ultrasound markers for LUTO. We performed a systematic literature review of studies reporting on fetuses with hydronephrosis or a prenatally suspected and/or postnatally confirmed diagnosis of LUTO. Bayesian bivariate random effects meta-analytic models were fitted, and we calculated posterior means and 95% credible intervals for the pooled diagnostic odds ratio (DOR). A total of 36,189 studies were identified; 636 studies were available for full text review and a total of 42 studies were included in the Bayesian meta-analysis. Among the ultrasound signs assessed, megacystis (DOR 49.15, [15.28, 177.44]), bilateral hydroureteronephrosis (DOR 41.33, [13.36,164.83]), bladder thickening (DOR 13.73, [1.23, 115.20]), bilateral hydronephrosis (DOR 8.36 [3.17, 21.91]), male sex (DOR 8.08 [3.05, 22.82]), oligo- or anhydramnios (DOR 7.75 [4.23, 14.46]), and urinoma (DOR 7.47 [1.14, 33.18]) were found to be predictive of LUTO (Table 1). The predictive sensitivities and specificities however are low and wide study heterogeneity existed. Classically, LUTO is suspected in the presence of prenatally detected megacystis with a dilated posterior urethra (i.e., the keyhole sign), and bilateral hydroureteronephrosis. However, keyhole sign has been found to have modest diagnostic performance in predicting the presence of LUTO in the literature which we confirmed in our analysis. The surprisingly low specificity may be influenced by several factors, including the degree of obstruction, and the diligence of the sonographer at searching for and documenting it during the scan. As a result, providers should consider this when establishing the differential for a fetus with hydronephrosis as the presence or absence of keyhole sign does not reliably rule in or rule out LUTO. Megacystis, bilateral hydroureteronephrosis and bladder wall thickening are the most accurate predictors of LUTO. Given the significant consequences of a missed LUTO diagnosis, clinicians providing counselling for prenatal hydronephrosis should maintain a low threshold for considering LUTO as part of the differential diagnosis.

Prenatal ultrasound diagnosis of Seckel syndrome with bi‐allelic variant in TRAIP via exome sequencing

We present two consecutive pregnancies with shared ultrasound findings-sloping forehead, micrognathia, ambiguous genitalia, brachycephaly, short extremities, single umbilical artery, choroid plexus cysts, and clenched hands. Subsequent whole exome sequencing identified TRAIP gene variants implicating diagnosis of Seckel syndrome 9 (SCKL9). Prenatal testing in subsequent pregnancy identified one variant. Our case highlights the utility of whole exome sequencing when prenatal ultrasound findings lend suspicion. Molecular confirmation allows for testing strategies in, or prior to, subsequent pregnancies. The finding of a rare, novel missense variant in TRAIP gene further implicates this mutation as having deleterious clinical manifestations.

Diagnosis of central nervous system abnormalities: comparison of prenatal neurosonography and foetal magnetic resonance imaging findings

Magnetic resonance imagining (MRI) is gradually becoming the more preferred imaging modality in the evaluation of central nervous system (CNS) abnormalities rather than foetal ultrasonography (USG). The aim of this study was to compare the findings of prenatal neurosonography and foetal MRI. The study was a retrospective study analysing the records of 160 pregnant women who underwent both foetal MRI and USG due to suspicion of CNS abnormalities between 2008 and 2019. Indications for applying foetal MRI were neurosonography and foetal MRI findings. When the compatibility between MRI and USG results was examined in CNS abnormalities, it was found fully compatible in 61.3% of cases, partially compatible in 24.53% of cases, and not compatible in 14.5% of cases. When comparing prenatal neurosonography and foetal MRI findings, additional findings were reported in 16.9% of cases, and no additional finding was reported in 66.8% of cases. While normal anatomical findings were reported in 8.8% of the cases in MRI, the diagnosis made by neurosonography changed in 7.5%. Foetal MRI has more advantages than USG both in imaging the CNS abnormalities in more detail and in determining the accompanying additional anomalies. IMPACT STATEMENT What is already known on this subject: USG is a safe, practical and cost-effective primary imaging method that is widely used for foetal anomaly screening. However, there may sometimes be difficulties in evaluating the foetal brain structures due to foetal position which is unsuitable for imaging, extremely obese with a high body mass index, oligohydramnios and ossified foetal skull. For this reason, magnetic resonance imaging (MRI) is used as the most commonly used imaging method after USG in the evaluation of foetal anatomy, especially CNS. What do the results of this study add?: In our study, we saw that foetal MRI has more advantages than neurosonography in both seeing CNS abnormalities in more detail and recognising additional anomalies that may accompany. What are the implications of these findings for clinical practice and/or further research?: We have seen that besides neurosonography, foetal MRI can provide important information that can affect the clinical approach in pregnancy management by increasing the correct diagnosis in pregnancies with congenital CNS abnormalities. MRI: it is the best secondary imaging modality that can aid diagnosis in addition to neurosonography in the diagnosis of CNS abnormalities and in suspected cases. Therefore, foetal MRI should be used more widely in prenatal diagnosis.