Implementation of fetal clinical exome sequencing: Comparing prospective and retrospective cohorts.

PURPOSE: We compared the diagnostic yield of fetal clinical exome sequencing (fCES) in prospective and retrospective cohorts of pregnancies presenting with anomalies detected using ultrasound. We evaluated factors that led to a higher diagnostic efficiency, such as phenotypic category, clinical characterization, and variant analysis strategy. METHODS: fCES was performed for 303 fetuses (183 ongoing and 120 ended pregnancies, in which chromosomal abnormalities had been excluded) using a trio/duo-based approach and a multistep variant analysis strategy. RESULTS: fCES identified the underlying genetic cause in 13% (24/183) of prospective and 29% (35/120) of retrospective cases. In both cohorts, recessive heterozygous compound genotypes were not rare, and trio and simplex variant analysis strategies were complementary to achieve the highest possible diagnostic rate. Limited prenatal phenotypic information led to interpretation challenges. In 2 prospective cases, in-depth analysis allowed expansion of the spectrum of prenatal presentations for genetic syndromes associated with the SLC17A5 and CHAMP1 genes. CONCLUSION: fCES is diagnostically efficient in fetuses presenting with cerebral, skeletal, urinary, or multiple anomalies. The comparison between the 2 cohorts highlights the importance of providing detailed phenotypic information for better interpretation and prenatal reporting of genetic variants.

Fetal kidneys: additional sonographic criteria of normal development.

OBJECTIVE: The aim of this study was to establish objective criteria for the evaluation of cortical echogenicity (CE), cortical thickness (CT), and medullary thickness (MT), as well as the corticomedullary ratio (CMR), throughout gestation. METHOD: In this prospective single-center study, CE, MT, CT, and CMR were evaluated in a group of singleton pregnancies examined by ultrasound during the second and third trimesters. RESULTS: The CE evolved from a hyperechoic pattern compared with the liver or spleen during early second trimester to a hypoechogenic pattern in the third trimester, with no fetus displaying cortical hyperechogenicity after 32 weeks. CT increased from 1.8 to 2.5 mm (p < 0.05) from 21 to 25 to 34 to 37 weeks; MT from 2.7 to 5.1 mm (p < 0.0001), and the CMR decreased from 0.7 to 0.5 (p < 0.001). CONCLUSION: The CE, CT, and MT evolve with gestation. Cortical hyperechogenicity compared with the liver or spleen after 32 weeks or a CMR above 0.7 in the third trimester should raise the suspicion of a fetal nephropathy.

Tumours of the fetal body: a review.

Tumours of the fetal body are rare, but lesions have been reported in all spaces, especially in the mediastinum, the pericardial space, the adrenals, the kidney, and the liver. Lymphangioma and teratoma are the commonest histological types encountered, followed by cardiac rhabdomyoma. Adrenal neuroblastoma is the commonest malignant tumour. Imaging plays an essential role in the detection and work-up of these tumours. In addition to assisting clinicians it also helps in counselling parents. Most tumours are detected by antenatal US, but fetal MRI is increasingly used as it brings significant additional information in terms of tumour extent, composition and complications.

Prepubertal Vulvar Fibroma: Neoplasm or Physiological Condition?

BACKGROUND: Several authors have previously reconsidered vulvar fibroma, a rare prepubertal neoplasm, as a physiological labial asymmetry of early puberty, recommending a conservative approach for all cases, although some required further clarification. CASE: A fibrous mass found in the left labium majus of a 4-year-old girl was surgically removed. Imaging confirmed a relapse after 10 months and a second surgery was performed due to extremely rapid growth. No subsequent relapse occurred after 2 years of follow-up. Diagnosis confirmed prepubertal vulvar fibroma, with positive CD34 and lack of actin, desmin, S100, and estrogen receptors. SUMMARY AND CONCLUSION: A diagnosis of prepubertal labial asymmetry should prompt careful consideration of several variables, such as age, and radiologic and histologic features, in order to differentiate between a physiological condition and a neoplasm.

Sonographic prenatal diagnosis of malpositioned stomach as a feature of uncomplicated intestinal malrotation.

Intestinal malrotation is a developmental anomaly affecting the position and peritoneal attachments of the small and large intestines during fetal life. Most often the diagnosis is established in the first year of life on the basis of abdominal pain and bile-stained vomiting secondary to bowel obstruction. The antenatal diagnosis can be suggested by identification of the complications such as bowel dilatation, ascites or meconium peritonitis. We describe two cases of isolated antenatal gastric malposition without any other associated anomaly that were confirmed after birth to be due to intestinal malrotation. We suggest that such an antenatal finding should alert the paediatrician to close clinical follow-up and prompt the diagnosis and surgical treatment in case of abdominal pain and/or bilious vomiting.

Perinatal assessment of hereditary cystic renal diseases: the contribution of sonography.

The aims of this review article were to clarify the steps that may lead to a proper diagnosis of fetal and neonatal renal cystic diseases. All the hereditary cystic diseases are reviewed and a classification is proposed. The various sonographic patterns that can be used to ascertain the diagnosis are also reviewed. Finally, tables with differential diagnoses are presented to help the reader in the work-up of such pathologies.

The iliac angle: a sonographic marker of trisomy 21 during the midtrimester: dependency of fetal lying?

The aim of this study was to evaluate the efficiency of the fetal iliac wing angle measurements in the detection of trisomy 21 during the second trimester and the impact of the fetal position on this measurement. During a 43-month period, the iliac wing angle was prospectively measured in 695 fetuses at genetic ultrasonography performed before amniocentesis. The iliac wing angle measurements were performed in a true axial section of the fetal pelvis and the relative position of the fetal spine was recorded (decubitus, lateral). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio (LR) were computed for multiple cutoff angles. The prevalence of trisomy 21 was 1.4%; 447 fetuses were in lateral position, 240 fetuses were in decubitus position, including, respectively, 2 and 8 fetuses with trisomy 21 (8 fetuses with other chromosomal anomalies were excluded). In euploid fetuses, the mean iliac wing angle was 83.7 degrees in decubitus and 68.7 degrees in lateral position; in fetuses with trisomy 21 the respective mean angles were 104.9 degrees and 102.5 degrees. A receiver operating characteristics (ROC) curve provided an absolute cutoff angle of 90 degrees, predicting trisomy 21 with a sensitivity of 100%, a specificity of 72.4%, an NPV of 100%, a PPV value of 11.1%, and an LR of 3.6. The measurement of iliac wing angles in an axial section of the fetal pelvis is dependent on spine orientation and provides an efficient cutoff angle for the exclusion of trisomy 21 in patients at risk.

Complementary role of MRI after sonography in assessing bilateral urinary tract anomalies in the fetus.

OBJECTIVE: The objectives of our study were to evaluate the contribution of adding MRI findings to inconclusive sonographic data when assessing fetal urinary tract anomalies and to determine how this addition may affect the management of pregnancy. SUBJECTS AND METHODS. We prospectively used MRI to study 16 third-trimester fetuses in whom sonography suggested bilateral urinary tract anomalies but failed to provide a definite diagnosis. These anomalies included enlarged hyperechoic kidneys (n = 6), bilateral pelvicaliceal dilatation (n = 6), renal cystic lesions (n = 2), and renal agenesis associated with severe oligohydramnios (n = 2). RESULTS: The addition of MRI to sonography modified the diagnosis in five fetuses. In a fetus with suspected bilateral ureteropelvic obstruction, the diagnosis of bilateral ureterohydronephrosis associated with reflux or ureterovesical junction obstruction was made. In a fetus with an enlarged bladder at 32 weeks' gestational age, a possible diagnosis of megacystic microcolon was excluded on the basis of the normal appearance of the colon. In two fetuses with enlarged hyperechoic kidneys, MRI showed localized medullary hyperintense lesions suggesting autosomal recessive polycystic kidney disease in one fetus and medullary cystic dysplasia in another fetus with Jeune's syndrome. In a patient with suspected unilateral renal agenesis, MRI showed bilateral agenesis. In four fetuses, the addition of MRI to sonography led to a diagnosis that modified the decision to continue or terminate the pregnancy. CONCLUSION: MRI can accurately show many urinary tract anomalies in third-trimester fetuses. It may be a useful complementary tool in the assessment of bilateral urinary tract anomalies of fetuses, particularly in cases with inconclusive sonographic findings.