Isolated Upward Rotation of the Fetal Cerebellar Vermis (Blake's Pouch Cyst) Is a Normal Variant: An Analysis of 111 Cases.

INTRODUCTION: The objective of the study was to provide more detailed data about fetal isolated upward rotation of the cerebellar vermis rotation (Blake's pouch cyst) in particular regarding pregnancy outcome. METHODS: This is a retrospective study of all cases of fetal isolated upward rotation of the cerebellar vermis (URCV) diagnosed in 3 referral centers in Italy from January 2009 to November 2019. Whenever possible, prenatal magnetic resonance imaging (MRI) was performed and a fetal karyotype was obtained. A detailed follow-up was obtained by consultation of medical records, interview with the parents, and the pediatricians. RESULTS: Our study population included 111 patients with a prenatal diagnosis of isolated URCV made at a median gestational age of 21 weeks +3 days (interquartile range (IQR) 21 + 0-22 + 2). The median brain stem-vermis (BV) angle was 27° (IQR 24-29°). In 37.9% of the cases, a regression of the finding with restoration of normal anatomy was noted at a follow-up scan or at postnatal checks. A BV angle of 25° or less predicted regression with a probability in excess of 90%. MRI was performed in utero or at birth in 101 patients and always confirmed sonographic diagnosis. Fetal CGH array and/or karyotype was available in 97 cases and was always normal, but in 1 case. A postnatal follow-up was available in 102 infants (mean 7 months, range 0-10 years of age) and documented a normal neurologic development in all the cases. CONCLUSIONS: Isolated URCV is most likely a normal variant of fetal anatomy without clinical consequences, at least at an early follow-up. A BV angle of 25° or less predicts intrauterine regression of the finding, but the outcome is good in all the cases. When a confident sonographic diagnosis is made, MRI is not mandatory. The risk of a chromosomal anomaly in these cases is probably low.

Functional evidence of mTORß splice variant involvement in the pathogenesis of congenital heart defects.

mTOR dysregulation has been described in pathological conditions, such as cardiovascular and overgrowth disorders. Here we report on the first case of a patient with a complex congenital heart disease and an interstitial duplication in the short arm of chromosome 1, encompassing part of the mTOR gene. Our results suggest that an intragenic mTOR microduplication might play a role in the pathogenesis of non-syndromic congenital heart defects (CHDs) due to an upregulation of mTOR/Rictor and consequently an increased phosphorylation of PI3K/AKT and MEK/ERK signaling pathways in patient-derived amniocytes. This is the first report which shows a causative role of intragenic mTOR microduplication in the etiology of an isolated complex CHD.

Prospective detection and differential diagnosis of cystic posterior fossa anomalies by assessing posterior brain at 11-14 weeks.

BACKGROUND: The role of the first-trimester scan has expanded from aneuploidy screening to the diagnosis of fetal malformations. Abnormal appearance of the posterior brain at 11-14 weeks gestation is a marker of cerebral anomalies; in fact an increased amount of fluid, particularly when the choroid plexus of the fourth ventricle is not visible and only 2 brain spaces instead of 3 are seen, may indicate the presence of cystic or cyst-like posterior fossa anomalies, such as Blake's pouch cyst or Dandy-Walker malformation. OBJECTIVE: The purpose of this study was to assess the role of ultrasound scanning in the identification of cystic posterior fossa anomalies at 11-14 weeks gestation. STUDY DESIGN: A prospective cohort study of fetuses with cystic appearance of the posterior fossa at 11-14 weeks gestation was performed. In all cases and in a control group of 40 normal fetuses, the brainstem-tentorium angle was also measured. The presence or absence of cystic posterior anomalies was determined at birth or at postmortem evaluation. RESULTS: In the period 2014-2018, 32 fetuses with an increased brainstem-occipital bone distance and/or failure to visualize the choroid plexus of fourth ventricle (2 brain spaces) were seen. Of these, 18 fetuses were terminated in the first trimester because of associated anomalies and were excluded from the study because of unavailable autoptic findings. The remaining 14 fetuses eventually were found to have a Dandy-Walker malformation in 4 cases, a Blake's pouch cyst in 8 cases, and normal brain anatomy in 2 cases. Two brain spaces were seen in all cases with Dandy-Walker malformation and in 2 of 8 cases with Blake's pouch cyst. Both brainstem-occipital bone measurement and brainstem-tentorium angle were significantly different in fetuses with Dandy-Walker malformation, Blake's pouch cyst, and control subjects (P<.0001). The brainstem-occipital bone z-scores of fetuses with Dandy-Walker malformation and Blake's pouch cyst were always +3 or more and +1.7 or more, respectively. The brainstem-tentorium angle z-scores were always -5 or less and -0.1 or less, respectively. CONCLUSION: Our study confirms that sonography of the posterior brain at 11-14 weeks gestation allows the identification of cystic posterior fossa anomalies. A large brainstem-occipital bone predicts Dandy-Walker malformation or Blake's pouch cyst. The presence of 2 brain spaces and a small brainstem-tentorium angle are correlated significantly with the presence of Dandy-Walker malformation.

Risk of Fetal Loss in Pregnancies Undergoing Midtrimester Amniocentesis after Inconclusive Chorionic Villus Sampling.

OBJECTIVE: To estimate the procedure-related risk of miscarriage in pregnancies undergoing amniocentesis (AC) following inconclusive results for a chorionic villus sampling (CVS). METHODS: This was a multicentric retrospective cohort study of patients in which both CVS at 11-13 weeks' gestation and AC at 16-22 weeks were performed between January 1st, 2008, and July 31st, 2017. The primary outcome measure was pregnancy loss prior to 24 weeks gestation; the secondary one was intrauterine demise after 24 weeks. RESULTS: A total of 287 patients underwent transabdominal CVS and AC. Nine patients were lost at follow-up; therefore, the analysis was conducted on a population of 278 patients (275 singletons and 3 dichorionic twin pregnancies). AC was performed because of placental mosaicism (93.6%), failure of direct/semidirect preparation of trophoblastic cells (3.2%), or targeted genetic testing after the diagnosis of an anomaly in the second trimester (3.2%). In continuing pregnancies, there were no fetal losses prior to 24 weeks' gestation. Two intrauterine demises (including 1 fetus with multiple anomalies and growth restriction) in the third trimester were recorded. CONCLUSION: Patients undergoing midtrimester AC because of an inconclusive result of CVS can be reasonably reassured that in general the risk of miscarriage and fetal loss following the procedure is very small.

Diagnosis of congenital heart disease by early and second-trimester fetal echocardiography.

OBJECTIVES: The aim of this study was to compare the cardiac findings at 11 to 14 weeks' gestation with the second-trimester findings to evaluate the reliability of first-trimester echocardiography and the possibility of congenital heart disease evolution. METHODS: The database of our fetal medicine unit was searched for all patients who had undergone fetal echocardiography at 11 to 14 and 18 to 22 weeks' gestation from 2005 to 2010. In all of the antenatally suspected cases of congenital heart disease, the diagnosis was established conclusively by postnatal echocardiography, surgery, or autopsy. RESULTS: Among the 870 fetuses included in the study, 802 were considered to have no abnormalities on both examinations. Thirty-six cases had abnormal findings on both examinations, and 32 had discordant findings. Among the 32 discordant findings, 6 cases had a false-positive diagnosis of congenital heart disease on early echocardiography, and 26 had a different diagnosis. In 14 of these 26 cases, the diagnosis was slightly different on the second-trimester examination, or the defect misdiagnosed in the first trimester was a minor one. In 6 of the remaining 12 fetuses, a major congenital heart disease was missed on the early echocardiography. In 6 cases, the congenital heart disease developed or progressed in severity in the second trimester. CONCLUSIONS: First-trimester echocardiography is feasible and seems to allow considerably earlier detection of major congenital heart disease. However, it should be kept in mind that although most forms of heart defects can be diagnosed early in pregnancy, some may develop and become apparent only later in gestation.

Prenatal diagnosis and outcome of isolated vascular rings.

The purpose of this study was to describe our experience in the ultrasound visualization and management of prenatally diagnosed isolated vascular rings. From January 2002 to December 2007, a total of 19 fetuses had a sonographic diagnosis of isolated vascular rings in 2 reference centers at a mean gestational age of 23 weeks. There were 8 cases of left aortic arch with aberrant right subclavian artery, 5 cases of double aortic arch, and 6 cases of right aortic arch with aberrant left subclavian artery. Two fetuses had associated trisomy 21 and 1 had a 22q11 microdeletion. Parents chose to terminate the pregnancy in all cases. Four patients successfully underwent surgical correction, and in 1 patient, tracheoplasty was also performed. In conclusion, isolated vascular rings can be accurately diagnosed prenatally by using the "3-vessel and trachea view" and "supra-aortic-branch view" that allow detection of vascular structures running around the trachea. Karyotyping and prenatal testing for 22q11 microdeletions should be offered to all parents. Affected children should undergo surgical correction as soon as symptoms of tracheal compression appear, avoiding tracheomalacia. Associated congenital tracheal stenosis should be excluded before surgery.

Prenatal diagnosis and postnatal outcome of cardiac rhabdomyomas.

AIMS: To evaluate the sonographic appearance of suspected fetal cardiac rhabdomyomas and their evolution until delivery and in the postnatal period. METHODS: The study group consisted of 6 patients at 23-37 weeks of gestation referred to our Ultrasonic Unit, between March 1992 and December 1998, for suspected fetal cardiac rhabdomyomas. RESULTS: The cardiac tumors were single in three cases and multiple in the other cases. The size ranged from 11 to 47 mm. In two cases the tumors arose from the right ventricle, in one case from the interventricular septum and in three cases from the left ventricle. Five infants are alive and in satisfactory hemodynamic compensation, but three of them developed tuberous sclerosis. In two infants a regression in the maximum diameter of the tumor masses has been observed. One child underwent surgical treatment at the age of six months and the baby died after surgery. CONCLUSIONS: Two-dimensional and Doppler echocardiography are useful non invasive methods to diagnose fetal cardiac rhabdomyomas and to monitor their influence on the fetal cardiac function. However they do not allow us to recognize which fetuses presenting with features compatible with rhabdomyomas will develop tuberous sclerosis.