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ObjectiveBCORL1, a transcriptional co-repressor, has a role in cortical migration, neuronal differentiation, maturation, and cerebellar development. We describe BCORL1 as a new genetic cause for major brain malformations.Methods and resultsWe report three patients from two unrelated families with neonatal onset intractable epilepsy and profound global developmental delay. Brain MRI of two siblings from the first family depicted hypoplastic corpus callosum and septal agenesis (ASP) in the older brother and unilateral perisylvian polymicrogyria (PMG) in the younger one. MRI of the patient from the second family demonstrated complete agenesis of corpus callosum (CC). Whole Exome Sequencing revealed a novel hemizygous variant in NM_021946.5 (BCORL1):c.796C>T (p.Pro266Ser) in the two siblings from the first family and the NM_021946.5 (BCORL1): c.3376G>A; p.Asp1126Asn variant in the patient from the second family, both variants inherited from healthy mothers. We reviewed the patients' charts and MRIs and compared the phenotype to the other published BCORL1-related cases. Brain malformations have not been previously described in association with the BCORL1 phenotype. We discuss the potential influence of BCORL1 on brain development.ConclusionsWe suggest that BCORL1 variants present with a spectrum of neurodevelopmental disorders and can lead to major brain malformations originating at different stages of fetal development. We suggest adding BCORL1 to the genetic causes of PMG, ASP, and CC dysgenesis.

Background/Objectives: This study aimed to explore a relationship between the fetal subarachnoid space (SAS) width and various fetal pathologies, employing fetal brain MRI scans. Methods: A retrospective collection of fetal brain MRI scans of 78 fetuses was performed with sonographic indications of microcephaly, macrocephaly, or fetal growth restriction (FGR), during a 7-year period at a single tertiary center. The SAS width (named the SAS index) was manually measured in millimeters in ten specific anatomical locations (four in the axial plane and six in the coronal plane), and then converted to centiles by comparing it to (previously collected) data of apparently healthy fetuses. We evaluated the median SAS centiles using the Kruskal–Wallis and Mann–Whitney U tests for statistical comparison. Results: Seventy-eight subjects (mean gestational age of MRI scan 34.2 ± 2.2 weeks) were evaluated. The median SAS centiles were consistently higher in the macrocephaly group compared to the microcephaly group in all ten anatomical locations (statistically significant except coronal left inferior temporal gyri). Most pronounced difference was displayed in the insula gyri (axial and coronal). The median SAS centiles were higher in the microcephaly group when compared with FGR across all ten anatomical locations (all were statistically significant except for coronal frontal and insula gyri), and the maximal difference was found in the frontal gyri of both planes. The median SAS indexes (IQR) of the three groups in millimeters: macrocephaly 91.55 (86.35–101.05), microcephaly 59.46 (50.00–66.91), and FGR 53.21 (49.71–59.10), p < 0.001. Conclusions: We found a statistically significant association between the fetal subarachnoid space and various fetal pathologies: macrocephaly, microcephaly, and FGR. [ABSTRACT FROM AUTHOR]

Aim Method Results Interpretation To evaluate the role of parental magnetic resonance imaging (MRI) in assessing fetuses with suspected brain anomalies and its use in prenatal counselling.A retrospective, multicentre chart review was conducted on fetuses who underwent brain MRI because of suspected brain abnormalities between January 2008 and December 2022, with one or both parents who underwent brain MRI (MRI‐Trio) as part of prenatal counselling. Clinical and demographic data were collected, including fetal and parental MRI findings, prenatal counselling outcomes, genetic testing results, family and previous pregnancy history, neurological examinations of the born children up to 24 months of age, and autopsy reports of fetuses from terminated pregnancies. MRI‐Trio concordance was defined as at least one abnormal brain feature identified with similarity in the fetus and the parents. The live‐born children were assessed postnatally through either neurodevelopmental evaluations or telephone interviews.Sixty pregnancies were included (41.7% with concordant and 58.3% with discordant MRI‐Trio). Forty‐two children were born (70%) and 17 pregnancies were terminated (28.3%). One case of in utero fetal death (1.7%) was reported. The most common brain findings were multiple anomalies (n = 26, 43.3%), isolated disorders of the corpus callosum (n = 17, 28.3%), atypical periventricular pseudocysts (n = 6, 10%), and anomalies of the anterior complex (n = 4, 6.7%). MRI‐Trio enabled better prognostication. When MRI‐Trio was concordant, counselling was more favourable (n = 22, 36.6%) and the majority of live‐born children exhibited typical development (p < 0.001).MRI‐Trio is a valuable tool for identifying dominantly inherited brain anomalies that may not hold developmental significance or are associated with favourable outcomes, acknowledging the potential for variable penetrance, which may result in more severe presentations. Concordant MRI‐Trio findings can enhance the accuracy of prenatal counselling, potentially reducing the incidence of termination of pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: Fetal growth assessment is a key component of prenatal care. Sex-specific fetal brain nomograms on ultrasound are available and are clinically used. In recent years, the use of fetal MRI has been increasing; however, there are no sex-specific fetal CNS nomograms on MRI. The study aimed to assess the differences in fetal brain biometry and growth trajectories and to create population-based standards of the fetal brain on MRI. Methods: In this cross-sectional study, brain structures of singleton fetuses with normal brain MRI scans were analyzed: biparietal diameter, occipitofrontal diameter, trans-cerebellar diameter, and the corpus callosum were measured and converted into centiles. Sex-specific nomograms were created. Results: A total of 3848 MRI scans were performed in one tertiary medical center between 2011 and 2019; of them, 598 fetuses met the inclusion criteria, 300 males and 298 females between 28- and 37-weeks' gestation. Males had significantly larger occipitofrontal diameter than females (median 75%, IQR 54–88%; median 61%, IQR 40–77%) and biparietal diameter (median 63%, IQR 42–82%; median 50%, IQR 25–73%), respectively (p < 0.001). The cerebellum had the greatest growth rate, with a 1.5-fold increase in diameter between 28 and 37 weeks' gestation, with no measurement difference between the sexes (p = 0.239). No significant difference was found in the corpus callosum (p = 0.074). Conclusion: Measuring both sexes on the same nomograms may result in over-estimation of male fetuses and under-estimation of females. We provide fetal sex-specific nomograms on two-dimensional MRI. [ABSTRACT FROM AUTHOR]

Aim: To assess whether microcephaly with pontine and cerebellar hypoplasia (MICPCH) could manifest in the prenatal period in patients with calcium/calmodulin‐dependent serine protein kinase (CASK) gene disorders. Method: In this international multicentre retrospective study, we contacted a CASK parents' social media group and colleagues with expertise in cerebellar malformations and asked them to supply clinical and imaging information. Centiles and standard deviations (SD) were calculated according to age by nomograms. Results: The study consisted of 49 patients (44 females and 5 males). Information regarding prenatal head circumference was available in 19 patients; 11 out of 19 had a fetal head circumference below –2SD (range −4.1SD to −2.02SD, mean gestational age at diagnosis 20 weeks). Progressive prenatal deceleration of head circumference growth rate was observed in 15 out of 19. At birth, 20 out of 42 had a head circumference below –2SD. A total of 6 out of 15 fetuses had a TCD z‐score below –2 (range −5.88 to −2.02). Interpretation: This study expands the natural history of CASK‐related disorders to the prenatal period, showing evidence of progressive deceleration of head circumference growth rate, head circumference below –2SD, or small TCD. Most cases will not be diagnosed according to current recommendations for fetal central nervous system routine assessment. Consecutive measurements and genetic studies are advised in the presence of progressive deceleration of head circumference growth rates or small TCD. What this paper adds: Progressive deceleration of fetal head circumference growth rate can be observed.A small transcerebellar diameter is an additional important manifestation.Most cases will not be diagnosed according to current recommendations for fetal central nervous system routine assessment.Consecutive measurements are advised when measurements are within the low range of norm. [ABSTRACT FROM AUTHOR]

To characterize the biometric parameters in ultrasound and brain MRI of fetuses with isolated mega cisterna magna (MCM). Cross-sectional historical cohort study conducted at a single tertiary medical center between 2011 and 2018. All fetuses underwent US and brain MRI scans. Matching analysis was performed according to gender and gestational age. The study included a total of 103 fetuses; 44 fetuses with isolated MCM in the study group, and a control group of 59 fetuses with normal CNS. The study group had larger biparietal diameter (BPD) (86 vs. 79.8 mm, p =.001) and head circumference (HC) (318 vs. 292 mm, p <.001) on ultrasound. On MRI, study group had larger occipitofrontal diameter (OFD) (99 vs. 92 mm, p <.001) and BPD (77 vs. 72 mm, p <.001). Male fetuses' prevalence was higher in the study group (77.3% vs. 47.5%). After matching 20 fetuses from each group, the study group had larger HC (310.1 versus 300.7 mm, p =.029) and OFD (113.4 versus 108.3 mm, p =.009) on ultrasound, and larger OFD (97.4 versus 94.6, p =.013) on brain MRI. Isolated MCM may be related to other large fetal CNS biometric measurements in both ultrasound and MRI and might be influenced by fetal gender. [ABSTRACT FROM AUTHOR]

Objective The representation of women among authors of peer reviewed scientific papers is gradually increasing. The aims of this study were to examine the trend of the proportion of women among authors in the field of rheumatology during the last two decades. Methods Articles published in journals ranked in the top quartile of the field of rheumatology in the years 2002–2019 were analysed. The authorship positions of all authors, country of the article's source and manuscript type were retrieved by specifically designed software. Results Overall, 153 856 author names were included in the final analysis. Of them, 55 608 (36.1%) were women. There was a significant rise in the percentage of women authors over time (r  = 0.979, P  <0.001) from 30.9% in 2002 to 41.2% in 2018, with a slight decline to 39.8% in 2019. There were significantly fewer women in the senior author positions compared with the first author positions (24.3% in senior position vs 40.9% as first author, P  <0.001). Conclusion The proportion of women among authors of rheumatology articles has increased over the years, both in general and as a first or senior author; however, their proportion is still <50% and there is still a gap between the proportion of women among first authors and the proportion of women among senior authors. [ABSTRACT FROM AUTHOR]

Introduction: The subarachnoid space (SAS) is a potential space surrounding the brain where the cerebrospinal fluid (CSF) flows. Previous work demonstrated how the SAS width changes during pregnancy and measured the normal values per gestational week., Objectives: Studying the ratio between the fetal brain volume (STV) and the SAS width (SS ratio), as measured via fetal magnetic resonance imaging (MRI) in different fetal pathologies - macrocephaly and microcephaly, and studying the correlation between this ratio and the gestational week., Methods: A retrospective study was conducted on 77 fetuses that underwent fetal MRI scans during gestational weeks 29-37, in three groups: 23 normocephaly, 27 macrocephaly, and 27 microcephaly. SAS width was measured in 10 points via fetal MRI scans, and a ratio was calculated between the width and STV., Results: The SS ratio is largest in microcephaly group and smallest in normocephaly group, with the macrocephaly group between them. All comparisons were statistically significant except between the macrocephaly and normocephaly groups. There was a strong positive correlation between SS ratio and week of gestation., Conclusions: The SS ratio is statistically different between normocephalic fetuses and fetuses with macrocephaly or microcephaly. From week 29 this ratio enlarges with gestational age., Discussion: The SAS affects the fetal head circumference, an important parameter of fetal growth, thus we decided to study the SS ratio in pathologies of the head circumference. Previous work demonstrated how the STV and the SAS width expand starting at a specific gestational age, thus the gestational week also affects the SS ratio. Summary: The SS ratio is affected by pathologies of the fetal head circumference and by gestational age.