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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 ≤ 5th 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. [ABSTRACT FROM AUTHOR]

Objective: To construct a reference range for a new vertical measurement of the fetal head and to assess whether its combination with fetal head circumference (HC) can prevent the misdiagnosis of microcephaly in fetuses with an acrocephalic-like head deformation.Methods: A new vertical cranial biometric measurement was defined: the foramen magnum-to-cranium distance (FCD), measured between the foramen magnum and the upper inner cranial border along the posterior wall of the brainstem. The measurement was performed in a precise mid-sagittal plane using a three-dimensional multiplanar display of a sagittally acquired sonographic volume of the fetal head. The normal reference range was developed by measuring 396 healthy fetuses of low-risk singleton pregnancies between 15 and 40 gestational weeks. This reference was applied to 25 fetuses with microcephaly diagnosed prenatally (Fmic) based on HC ≥ 3 SD below the mean for gestational age. We determined an optimal FCD cut-off for combination with HC to detect all cases found with microcephaly at birth (micB), while excluding the fetuses with normal head circumference at birth (NHCB), who were described postnatally as having an acrocephalic-like cranial deformation.Results: In the healthy singleton fetuses, FCD increased with gestational age, with a quadratic equation providing an optimal fit to the data (adjusted R(2) = 0.934). The measurement could be assessed in 95.2% of cases. Of the 25 cases diagnosed with Fmic prenatally, on the basis of HC alone, 14 were micB and 11 were NHCB. We observed FCD below the mean - 2SD for gestational age in all 14 micB cases, but in only four of the 11 NHCB cases (P < 0.003). An acrocephalic-like cranial deformation was described at birth in five of the seven NHCB cases with normal FCD. The mean ± SD FCD Z-score of the micB cases was significantly lower (P < 0.001) than that of the false-positive ones: -3.85 ± 0.96 SD and -1.59 ± 1.45 SD, respectively. Based on HC measurement alone, the positive predictive value (PPV) was 56%. Combination of the HC and FCD criteria raised the PPV to 78%, decreasing the number of false positives from 11 to four, without missing any of the 14 micB cases.Conclusions: Fetal vertical cranial biometric assessment in the mid-sagittal plane is feasible and correlates well with gestational age. In our series, a vertical cranial deformation was a frequent cause of a false Fmic diagnosis made on the basis of HC alone. Combination of the new vertical cranial biometric measurement with HC measurement can exclude these cases and thus improve diagnostic accuracy for Fmic. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives To compare the outcomes of fetuses with apparently isolated macrocephaly and those with associated findings, and to compare prenatal findings with postnatal diagnoses in children with syndromic macrocephaly. Methods We reviewed the files of all patients referred for suspected fetal macrocephaly, during a 10-year period from 2000, to a large prenatal diagnosis unit with expertise in fetal neurology counseling. Macrocephaly was defined as head circumference (HC) > 2 SDs of the norm. Patients with confirmed HC > 2 SD were identified and contacted, and their development was evaluated. Results Adequate data for analysis were available for 98 patients, in 82 of whom the fetal macrocephaly was considered isolated (Group A), and in 16 of whom associated fetal anomalies were identified (Group B). Macrocephaly was diagnosed earlier in Group B patients (28.4 vs. 32.3 weeks, P = 0.069), and the HC in Group B patients was larger ( Z-score 2.95 vs. 2.3, P < 0.001). From Group A there were 81 liveborn; one of whom was diagnosed as having infantile autism. From Group B, there were nine liveborn. The associated central nervous system findings, as demonstrated by ultrasound and magnetic resonance imaging, included mild ventriculomegaly, malformations of cortical development, callosal abnormalities, overdeveloped sulcation, large cavum septi pellucidi, large subarachnoid spaces, mega cisterna magna, periventricular pseudocyst, open operculum and vermian dysgenesis. Syndromic diagnosis was made in utero in five fetuses and after birth in three. In eight patients, associated malformations were confirmed after birth but a specific diagnosis was not reached. Conclusions When fetal macrocephaly is associated with other brain or systemic anomalies, syndromic macrocephaly can be diagnosed in utero. Fetuses with syndromic macrocephaly have a significantly larger HC, usually > 2.5 SD above the mean. Isolated macrocephaly, particularly when the HC is < 2.5 SD above the norm, may be clinically benign. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents information on a study that evaluates the significance of a thick fetal corpus callosum. The methodology involves the review of records of fetuses with anomalies of the corpus callosum. Results show that cases have associated abnormalities like macrocephaly, ventriculomegaly, vermian agenesis, and abnormal sulcation. It concludes that a thick corpus callosum may be a sign of neurogenetic syndromes. Tables and figures elaborating the study are likewise shown.

Objective Malformations of cortical development (MCD) are rarely diagnosed in utero. We describe and compare the ultrasonographic and pathology findings in a cohort of fetuses with MCD. Methods Fetuses with MCD were identified among all fetuses evaluated for suspected brain anomalies at the Fetal Neurology Clinic, and the ultrasonographic findings were compared with the results of the pathology examination. Results We suspected the presence of MCD by ultrasonography in 23 fetuses. The mean gestational age at the time of ultrasound diagnosis was 26.2 (range, 18–40) weeks. The ultrasonographic findings leading to the diagnosis of MCD were abnormally overdeveloped gyri and sulci for gestational age (n = 7), delay in sulcation (n = 5), abnormally thin cortex (n = 5) abnormally wide and broad sulci (n = 3), bulging into the lateral ventricle (n = 1), cortical cleft (n = 1), and multiple intraparenchymal echogenic nodules (n = 1). All fetuses had associated central nervous system (CN8) and/or non-CNS anomalies. Pathology examination (performed in 17 fetuses) confirmed MCD in 16. Conclusions Cortical malformations can be diagnosed in utero by ultrasonography based on the presence of specific deviations from the normal pattern of development. The identified cases may represent the more severe forms in the MCD spectrum. The pathology findings do not always conform to the current classification systems of MCD but help in differentiating between possible genetic and acquired etiologies and in some cases provide a definitive syndromic diagnosis. [ABSTRACT FROM AUTHOR]

Objectives To evaluate whether fetal brain magnetic resonance imaging (MRI) adds useful clinical information to that obtained by dedicated fetal neurosonography using a combined transabdominal and transvaginal approach in fetuses with suspected brain anomalies. Methods In the 2-year period between January 2000 and January 2002, 42 fetuses underwent neurosonographic and MRI examinations of the brain. The referral indications were: asymmetric ventriculomegaly (13), ventriculomegaly (7), periventricular cysts (2), suspected midline findings (7), agenesis of the corpus callosum (3), infratentorial pathology (3), cytomegalovirus (CMV) infection (2) and miscellaneous indications (5). Results Neurosonography and MRI produced similar diagnoses in 29 fetuses: normal examination (10), isolated asymmetric ventriculomegaly (11), isolated ventriculomegaly (3), periventricular cysts (2), agenesis of the corpus callosum (1), pericallosal lipoma (1) and cerebellar hemorrhage (1). The neurosonographic diagnoses were more accurate in seven patients: hemimegalencephaly, pericallosal lipoma, signs of CMV infection, brain anomalies associated with agenesis of the corpus callosum and three fetuses with a normal ultrasound scan in which MRI suggested a parenchymal abnormality. MRI provided a more accurate diagnosis in three patients: a third ventricular dilatation was ruled out, normal ventricles in a fetus with an ultrasonographic finding of asymmetric ventricles, and diagnosis of progression of asymmetric ventriculomegaly. In three patients the identified pathologies were differently interpreted, each examination provided another aspect of the anomaly or a definitive diagnosis was not possible. Conclusions Our study demonstrated that dedicated neurosonography is equal to MRI in the diagnosis of fetal brain anomalies. In most of the cases MRI confirmed the ultrasonographic diagnosis; in a minority of cases each modality provided additional/different information. The major role of MRI was in reassurance of the parents regarding the presence or absence of brain anomalies. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Periventricular pseudocysts (PVPC) are diagnosed in approximately 1% of premature newborns that undergo brain sonography during the first 24 h of life. These pseudocysts are thought to develop antenatally due to germinal matrix hemorrhage, but have not been described until now in prenatal ultrasound studies. The aim of this study was to report the identification, differential diagnosis, and prognosis of PVPC detected by prenatal ultrasound examination. Design Between 1997 and 2001 we made an ultrasound diagnosis of PVPC in 11 fetuses. In nine fetuses the findings were characteristic of PVPC and these patients represent our study group. Fetal magnetic resonance imaging was performed in five patients. Termination of pregnancy was carried out in three patients, in one case intrauterine fetal death occurred at 31 weeks, and one infant died in the neonatal period. The surviving four newborns are being followed in the pediatric neurology clinic. Results PVPC were diagnosed by ultrasound scan in fetuses between 16 and 37 weeks of gestation (mean, 29.7 weeks). Magnetic resonance imaging confirmed the presence of PVPC in two cases. In eight cases the pseudocysts were unilateral and in one case bilateral. They were an isolated finding in five patients. Four of these fetuses were delivered at term and have normal neurological development at ages ranging from 6 to 25 months. All fetuses with additional pathologies (coarctation of the aorta, hemimegalencephaly, cytomegalovirus infection, hypoplasia of the vermis with dysmorphism) did not survive. Conclusions The prenatal diagnosis of PVPC warrants an extensive search for possible associated pathological findings. As an isolated finding, antenatal PVPC seem to carry a good prognosis. [ABSTRACT FROM AUTHOR]