UNASSIGNED: Fetal ultrasound has limitations, especially if the patient is obese or in cases with oligohydramnios. Magnetic resonance imaging (MRI) can then be used as a complement, but only few studies have focused on examinations in the second trimester.
UNASSIGNED: To validate MRI as a complement to diagnose fetal anomalies in the second trimester.
UNASSIGNED: This retrospective study retrieved data from January 2008 to July 2012 from the Fetal Medicine Unit and Department of Radiology at Uppsala University Hospital. Ultrasound and MRI findings were reviewed in 121 fetuses in relation to the final diagnosis, including postpartum follow-up and autopsy results.
UNASSIGNED: Of the 121 fetuses, 51 (42%) had a CNS anomaly and 70 (58%) a non-CNS anomaly diagnosed or suspected. MRI provided additional information in 21% of all cases without changing the management and revealed information that changed the management of the pregnancy in 13%. When a CNS anomaly was detected or suspected, the MRI provided additional information in 22% and changed the management in 10%. The corresponding figures for non-CNS cases were 21% and 16%, respectively. The proportion of cases with additional information that changed the management was especially high in patients with a BMI >30 kg/m2 (25%) and in patients with oligohydramnios (38%). In five cases in category III, false-positive ultrasound findings were identified.
UNASSIGNED: MRI in the second trimester complements ultrasound and improves diagnosis of fetal CNS- and non-CNS anomalies especially when oligohydramnios or maternal obesity is present.

BACKGROUND: Corpus callosal abnormalities (CCA) are midline developmental brain malformations and are usually associated with a wide spectrum of other neurological and non-neurological abnormalities. The study aims to highlight the diagnostic role of fetal MRI to characterize heterogeneous corpus callosal abnormalities using the latest classification system. It also helps to identify associated anomalies, which have prognostic implications for the postnatal outcome.
METHODS: In this study, retrospective data from antenatal women who underwent fetal MRI between January 2014 and July 2023 at Rush University Medical Center were evaluated for CCA and classified based on structural morphology. Patients were further assessed for associated neurological and non-neurological anomalies.
RESULTS: The most frequent class of CCA was complete agenesis (79.1%), followed by hypoplasia (12.5%), dysplasia (4.2%), and hypoplasia with dysplasia (4.2%). Among them, 17% had isolated CCA, while the majority (83%) had complex forms of CCA associated with other CNS and non-CNS anomalies. Out of the complex CCA cases, 58% were associated with other CNS anomalies, while 8% were associated with non-CNS anomalies. 17% of cases had both.
CONCLUSIONS: The use of fetal MRI is valuable in the classification of abnormalities of the corpus callosum after the confirmation of a suspected diagnosis on prenatal ultrasound. This technique is an invaluable method for distinguishing between isolated and complex forms of CCA, especially in cases of apparent isolated CCA. The use of diffusion-weighted imaging or diffusion tensor imaging in fetal neuroimaging is expected to provide further insights into white matter abnormalities in fetuses diagnosed with CCA in the future.

OBJECTIVE: To investigate genetic etiology and pregnancy outcomes of fetal central nervous system (CNS) anomalies.
METHODS: 217 fetuses with CNS anomalies were included in our cohort from January 2016 to December 2022. 124 cases received karyotyping and 73 cases simultaneously underwent copy number variant sequencing (CNV-seq). Dynamic ultrasound screening and pregnancy outcomes were followed up, including neonates\' neurodevelopmental outcomes.
RESULTS: (1) 20 types of CNS anomalies were revealed by ultrasound and the most common was ventriculomegaly. (2) 14 (11.3%) of 124 cases were found chromosomal abnormalities by karyotyping, and copy number variations (CNVs) were revealed in 13 (17.8%) of 73 cases by CNV-seq. Fetuses with non-isolated CNS anomalies had a higher detection rate (DR) of abnormal karyotypes and CNVs than those with isolated CNS anomalies (25.0% vs. 4.8%; 35.0% vs. 11.3%) (P < 0.05). And the DR of abnormal karyotypes was significantly higher in multiple CNS anomalies than in single CNS anomaly (16.7% vs. 2.8%, P < 0.05), while there were no significant differences in the DR of CNVs. (3) Through dynamic ultrasound, 12 cases were further found progression or additional malformations. (4) Pregnancy outcomes of 209 cases were obtained, including 136 (65.1%) live births, 3 (1.4%) intrauterine fetal deaths, and 70 (33.5%) terminated. Two neonatal deaths at 6 months and one infant with motor and intellectual disabilities were finally found after long-term follow-up.
CONCLUSIONS: Genetic analysis combined with dynamic ultrasound screening and multidisciplinary consultation plays an important role in evaluating the prognosis of fetal CNS anomalies, especially for those with multiple CNS or extracranial abnormalities.

Spondylo-epi-metaphyseal dysplasias with joint laxity, type 3 (SEMDJL3) is a genetic skeletal disorder characterized by multiple joint dislocations, caused by biallelic pathogenic variants in the EXOC6B gene. Only four individuals from two families have been reported to have this condition to date. The molecular pathogenesis related to primary ciliogenesis has not been enumerated in subjects with SEMDJL3. In this study, we report two additional affected individuals from unrelated families with biallelic pathogenic variants, c.2122+15447_2197-59588del and c.401T>G in EXOC6B identified by exome sequencing. One of the affected individuals had an intellectual disability and central nervous system anomalies, including hydrocephalus, hypoplastic mesencephalon, and thin corpus callosum. Using the fibroblast cell lines, we demonstrate the primary evidence for the abrogation of exocytosis in an individual with SEMDLJ3 leading to impaired primary ciliogenesis. Osteogenesis differentiation and pathways related to the extracellular matrix were also found to be reduced. Additionally, we provide a review of the clinical and molecular profile of all the mutation-proven patients reported hitherto, thereby further characterizing SEMDJL3. SEMDJL3 with biallelic pathogenic variants in EXOC6B might represent yet another ciliopathy with central nervous system involvement and joint dislocations.

Copeptin has been shown to be associated with central nervous system pathologies. The aim of this study was to investigate the relationship between serum CCP levels and central nervous system (CNS) anomalies. In this case-control study, those at 9-14 weeks of gestation serum levels of copeptin, were assessed in pregnant women whose foetuses subsequently developed CNS anomalies (group 1: n = 60) and compared with gestational age-matched pregnant women who exhibited normal pregnancy outcomes (group 2: n = 48). The mean copeptin levels were 1.58 ± 0.40 ng/mL and 1.11 ± 0.36 ng/mL in the CNS anomalies and control groups, respectively (p < .0001). An increased level of copeptin independently predicts development of CNS anomalies, suggesting that copeptin can be used for prediction and discrimination of CNS anomalies in normal pregnancies at 9-14 weeks of gestation.Impact statementWhat is already known on this subject? There is no test or method to diagnose CNS anomalies in the first trimester of pregnancy. This study presents the first and new information on the relationship between serum copeptin levels and central nervous system anomalies in pregnant women whose foetuses subsequently developed CNS anomalies.What do the results of this study add? I have strongly demonstrated differences in maternal CPP levels between CNS anomalous pregnancies and healthy controls.What are the implications of these findings for clinical practice and/or further research? It has been thought that copeptin appears to be an ideal marker for central nervous system anomaly prediction at 9-14 weeks of gestational age and if confirmed in larger prospective studies. Finally, these results could not be used as parameters for prenatal CNS screening. Advanced studies, well-structured and conducted on larger populations are needed to investigate the issue further.

Agenesis of corpus callosum (ACC) is an uncommon congenital anomaly, its etiology is unclear and its pathogenesis is controversial. Cases with ACC often have other non-ACC associated congenital anomalies. The purpose of this study was to assess the prevalence and the types of these associated anomalies in a defined population. The associated anomalies in cases with ACC were collected in all live births, stillbirths, and terminations of pregnancy during 29 years in 387,067 consecutive births in the area covered by our population-based registry of congenital malformations. Of the 99 cases with ACC, representing a prevalence of 2.56 per 10,000, 73 (73.7%) had associated anomalies. There were 16 (16.2%) cases with chromosomal abnormalities, and 13 (13.2%) nonchromosomal recognized dysmorphic conditions including syndromes two each: Aicardi, Dandy-Walker, and fetal alcoholism. Forty-four (44.4%) of the cases had nonsyndromic multiple congenital anomalies (MCA). Anomalies in the musculoskeletal, the urogenital, the central nervous, the cardiovascular, and the digestive systems were the most common other anomalies in the cases with MCA. The anomalies associated with ACC could be classified into a recognizable malformation syndrome in 29 out of the 73 cases (39.7%) with associated anomalies. This study included special strengths: it is population-based, each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for anomalies was continued until 2 years of age. In conclusion the overall prevalence of associated anomalies, three of four cases, emphasizes the need for a screening for other anomalies in cases with ACC.

Central nervous system (CNS) abnormalities are often isolated but can accompany various genetic syndromes. In this study, we evaluated conventional karyotype results and associated findings of fetuses that were diagnosed with CNS abnormalities. Cases included in the study were diagnosed with fetal CNS anomalies and underwent conventional karyotyping. Conventional karyotype results of subjects were compared with karyotype results of fetal karyotyped patients as a result of maternal anxiety in a two-year period. In this period, 69 patients were diagnosed with fetal CNS anomalies and 64 of them underwent invasive fetal karyotyping. Of these, 32 patients had isolated CNS anomalies, while 32 were associated with other anomalies. There was no significant difference between karyotype results when compared with the control group (p = 0.76). Apart from some specific anomalies, the aneuploidy rate does not significantly differ between fetuses with CNS anomalies and the control group. Advanced genetic evaluation may provide additional diagnostic benefits, especially for this group.