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Corpus callosum anomalies (CCA) is a common congenital brain anomaly with various etiologies. Although one of the most important etiologies is genetic factors, the genetic background of CCA is heterogenous and diverse types of variants are likely to be causative. In this study, we analyzed 16 Japanese patients with corpus callosum anomalies to delineate clinical features and the genetic background of CCAs. We observed the common phenotypes accompanied by CCAs: intellectual disability (100%), motor developmental delay (93.8%), seizures (60%), and facial dysmorphisms (50%). Brain magnetic resonance imaging showed colpocephaly (enlarged posterior horn of the lateral ventricles, 84.6%) and enlarged supracerebellar cistern (41.7%). Whole exome sequencing revealed genetic alterations in 9 of the 16 patients (56.3%), including 8 de novo alterations (2 copy number variants and variants in ARID1B, CDK8, HIVEP2, and TCF4) and a recessive variant of TBCK. De novo ARID1B variants were identified in three unrelated individuals, suggesting that ARID1B variants are major genetic causes of CCAs. A de novo TCF4 variant and somatic mosaic deletion at 18q21.31-qter encompassing TCF4 suggest an association of TCF4 abnormalities with CCAs. This study, which analyzes CCA patients usung whole exome sequencing, demonstrates that comprehensive genetic analysis would be useful for investigating various causal variants of CCAs., (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Biallelic mutations in the RTTN gene have been reported in association with microcephaly, short stature, developmental delay and malformations of cortical development. RTTN mutations have previously shown to link aberrant ciliary function with abnormal development and organization of the human cerebral cortex. We here report three individuals from two unrelated families with novel mutations in the RTTN gene. The phenotype consisted of microcephaly, short stature, pachygyria or polymicrogyria, colpocephaly, hypoplasia of the corpus callosum and superior vermis. These findings provide further confirmation of the phenotype related to pathogenic variants in RTTN., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Fetal lateral ventriculomegaly is a relatively common finding with much debate over its clinical significance. The purpose of this study was to examine the association between ventriculomegaly and asymmetry and concomitant CNS findings as seen in fetal brain MR imaging., Materials and Methods: Fetal brain MR imaging performed for various indications, including ventriculomegaly, with or without additional ultrasound findings, was assessed for possible inclusion. Two hundred seventy-eight cases found to have at least 1 lateral ventricle with a width of ≥10 mm were included in the study. Ventriculomegaly was considered mild if the measurement was 10-11.9 mm; moderate if, 12-14.9 mm; and severe if, ≥15 mm. Asymmetry was defined as a difference of ≥2 mm between the 2 lateral ventricles. Fetal brain MR imaging findings were classified according to severity by predefined categories., Results: The risk of CNS findings appears to be strongly related to the width of the ventricle (OR, 1.38; 95% CI, 1.08-1.76; P = .009). The prevalence of associated CNS abnormalities was significantly higher ( P = .005) in symmetric ventriculomegaly compared with asymmetric ventriculomegaly (38.8% versus 24.2%, respectively, for all CNS abnormalities and 20% versus 7.1%, respectively, for major CNS abnormalities)., Conclusions: In this study, we demonstrate that the rate of minor and major findings increased with each millimeter increase in ventricle width and that the presence of symmetric ventricles in mild and moderate ventriculomegaly was a prognostic indicator for CNS abnormalities., (© 2017 by American Journal of Neuroradiology.)

To clarify the pathogenesis of two different types of adult-onset normal-pressure hydrocephalus (NPH), we investigated cerebrospinal fluid distribution on the high-field three-dimensional MRI. The subarachnoid spaces in secondary NPH were smaller than those in the controls, whereas those in idiopathic NPH were of similar size to the controls. In idiopathic NPH, however, the basal cistern and Sylvian fissure were enlarged in concurrence with ventricular enlargement towards the z-direction, but the convexity subarachnoid space was severely diminished. In this article, we provide evidence that the key cause of the disproportionate cerebrospinal fluid distribution in idiopathic NPH is the compensatory direct CSF communication between the inferior horn of the lateral ventricles and the ambient cistern at the choroidal fissure. In contrast, all parts of the subarachnoid spaces were equally and severely decreased in secondary NPH. Blockage of CSF drainage from the subarachnoid spaces could cause the omnidirectional ventricular enlargement in secondary NPH.

Brain MRI scans revealed various occipital horn variants in a pedigreed baboon colony consisting of Papio hamadryas anubis and its hybrids. We retrospectively characterized these variants and evaluated their relationships to epilepsy phenotypes and scalp EEG findings. MRI scans (3D, T1-weighted) from 208 baboons (female, 134 female; male, 74; age [mean ± 1 SD], 16 ± 5 y) were reviewed; 139 (67%) of these animals also underwent scalp EEG previously. Occipital horn variants included elongation (extension of the occipital ventricle behind the mediobasal origin of the calcarine fissure), which affected 23 baboons (11%; 7 bilateral, 9 left, 7 right), and elongation with enlargement (colpocephaly), which occurred in 30 baboons (14%; 7 bilateral, 11 left, 12 right). The incidence of the occipital horn variants did not differ according to age or prenatal or perinatal history. Colpocephaly was associated with craniofacial trauma but not with witnessed seizures. Abnormal scalp EEG findings, including interictal epileptic discharges, did not differ significantly among the occipital horn morphologies. This study is the first radiologic description of occipital horn variants, particularly colpocephaly, in baboons. Whereas colpocephaly is frequently associated with other radiologic and neurologic abnormalities in humans, it is mostly an isolated finding in baboons. Because craniofacial trauma can occur in the setting of seizure-related falls, its increased association with colpocephaly may reflect an increased risk of seizures or of traumatic brain injuries due to seizures. Colpocephaly in baboons needs to be characterized prospectively radiologically, neurologically, histopathologically, and genetically to better understand its etiology and clinical significance.

Absent circle of Willis (COW) has been described in cases of severe forms of cerebral developmental anomalies such as alobar prosencephaly. However, there are no reports of absent COW in patients with a milder form of cerebral abnormality such as colpocephaly. We report a unique case of an adult with colpocephaly and absent COW and discuss their association from a developmental perspective., (© The Author(s) 2015.)

Background: Agenesis of the corpus callosum (ACC) is a developmental brain malformation associated with a wide spectrum of structural brain abnormalities and genetic loci. To characterize the diverse callosal morphologies and malformations of brain development associated with ACC, we report on the neuroimaging findings of 201 individuals diagnosed with corpus callosal abnormalities., Methods: We searched through medical records of individuals seen at New York Presbyterian Hospital between 2002 and 2013 and thought to have ACC. We confirmed 201 individuals meeting criteria and used magnetic resonance imaging to characterize morphological variants of the corpus callosum and associated brain malformations., Results: The majority of individuals displayed hypoplasia or dysplasia of the corpus callosum (N = 160, 80 %). Forty-one (20 %) displayed complete agenesis of the corpus callosum with other abnormalities, while only 18 (9 %) displayed complete agenesis without associated brain abnormalities. White matter abnormalities were more frequent in hypoplasia or dysplasia group than complete agenesis (28.2 % vs 9.8 %, p < 0.05). In contrast, hippocampal abnormalities, colpocephaly, and Probst bundles were significantly more frequent in complete agenesis compared to hypoplasia or dysplasia group., Conclusions: Collectively, our results underscore the broad diversity of morphological variants of the corpus callosum and associated brain abnormalities in individuals with ACC.

A case of dumbbell nasal and intracerebral olfactory neuroblastoma (ONB) related to possible seeding through an "olfactory ventricle" in the olfactory bulb and nerve is reported. This anatomic variant was recognized at operation for the first time: it consists of a hollow cavity within the olfactory bulb and nerve which may be connected to the subventricular zone of the frontal horn of the lateral ventricle. Better scrutiny of this structure is necessary in view of its possible interference with the course and diffusion of ONBs.

Objectives: The finding of fetal ventriculomegaly is variably associated with other fetal abnormalities and, even when isolated, is thought to be linked to abnormal neurodevelopmental outcome. The aim of this study was to undertake a systematic review and meta-analysis of the current literature to assess the prevalence of neurodevelopmental delay in cases of isolated mild fetal ventriculomegaly, as well as the false-negative rate of prenatal imaging for the diagnosis of associated abnormalities in patients referred for isolated mild ventriculomegaly., Methods: Studies that assessed neurodevelopmental outcome in isolated ventriculomegaly were identified from a search of scientific databases. Studies that did not check for karyotype or that excluded cases of bilateral ventriculomegaly were not included in the analysis. Ventriculomegaly was defined as mild when the width of the ventricular atrium was between 10 and 15 mm. Cases in which an associated abnormality (abnormal karyotype, structural abnormality or fetal infection) was observed either before or after birth were not considered as part of the isolated group. Neurodevelopmental delay was defined as an abnormal quotient score, according to the test used., Results: The search yielded 961 possible citations; of these, 904 were excluded by review of the title or abstract as they did not meet the selection criteria. Full manuscripts were retrieved for 57 studies, and 20 were included in the review with a total of 699 cases of isolated mild ventriculomegaly. The overall prevalence of neurodevelopmental delay was 7.9% (95% CI, 4.7-11.1%). Of the 20 studies included in the systematic review, nine reported data on postnatal imaging, showing a prevalence of previously undiagnosed findings of 7.4% (95% CI, 3.1-11.8%)., Conclusions: The false-negative rate of prenatal imaging is 7.4% in apparently isolated fetal ventriculomegaly of ≤ 15 mm. The incidence of neurodevelopmental delay in truly isolated ventriculomegaly of ≤ 15 mm is 7.9%. As the latter rate is similar to that noted in the general population, large prospective cohort studies assessing the prevalence of childhood disability, rather than subtle neurodevelopmental delay, are required., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Background: Owing to the number of genetic mutations that contribute to malformations of cortical development, identification of causative mutations in candidate genes is challenging. To overcome these challenges, we performed whole-exome sequencing in this study., Case Presentation: A Japanese patient presented with microcephaly and severe developmental delay. Brain magnetic resonance imaging showed the presence of colpocephaly associated with lateral ventricle dilatation and the presence of a simplified gyral pattern. Hypoplasia of the corpus callosum and cerebellar vermis were also noted. Because Sanger sequencing is expensive, laborious, and time-consuming, whole-exome sequencing was performed and a de novo missense mutation in TUBA1A (E27Q) was identified., Conclusion: The novel mutation identified in this study was located in the genetic region that encodes the N-terminal domain of TUBA1A, a region of TUBA1A with few reported mutations. Retrospective assessment of the clinical and radiological features of this patient-i.e., microcephaly, lissencephaly (pachygyria) with cerebellar hypoplasia, and corpus callosum hypoplasia-indicated that the TUBA1A mutation did not lead to any contradictions. Because rapid and comprehensive mutation analysis by whole-exome sequencing is time- and cost-effective, it might be useful for genetic counseling of patients with sporadic malformations of cortical development.

The cavum velum interpositum (CVI) is a thin, triangular-shaped cerebrospinal fluid (CSF)-filled space between the lateral ventricles that lies below the fornices and above the third ventricle. It is a normal variant seen in premature and newborn infants and usually disappears with brain maturation. CVI is rarely seen in adults as a persistent primitive structure. Although moderate cystic dilatation of the CVI may sometimes be observed, a true large cyst is extremely rare with only a handful of reported cases, mostly in children and adolescents. We describe the case of CVI arachnoid cyst diagnosed on imaging in a septuagenarian with the complaint of occasional headaches.

Objectives: To assess the presence and degree of indirect signs of agenesis of the corpus callosum (ACC) according to gestational age and determine the percentage of cases in which each sign is present by 24 gestational weeks., Methods: We analyzed retrospectively 54 cases of ACC which underwent three-dimensional neurosonography at our unit between January 2005 and December 2012. A single examination was available in 48 cases and six cases were followed up longitudinally, giving a total of 69 examinations. The following variables were assessed: indication for referral, karyotype, width of the atrium and presence/absence of colpocephaly, the cavum septi pellucidi, dorsal cyst and additional central nervous system (CNS) and non-CNS anomalies., Results: Overall, there were 31 cases of complete ACC (cACC, 42 examinations) and 23 cases of partial ACC (pACC, 27 examinations). The mean gestational age was lower in the cases referred because of anomalies other than ACC than it was in those referred because of ventriculomegaly and/or suspicion of ACC (P < 0.05). Atrial width showed a positive linear correlation with advancing gestational age (P < 0.0001); it was < 10.0 mm in 25/34 (73.5%) examinations < 24 gestational weeks and in 9/35 (25.7%) ≥ 24 weeks (P < 0.001). Colpocephaly was present in 20.6% (7/34) of examinations < 24 weeks and in 68.6% (24/35) of those after 23 weeks (P < 0.05). The cavum septi pellucidi was present and visible at least in part in 17 (63%) of the 27 pACC examinations. In nine of the 27 (33.3%) pACC examinations, there was neither ventriculomegaly nor absence of the cavum septi pellucidi. Associated anomalies were present in 25/54 (46.3%) cases, and in 11 these included or consisted of CNS abnormalities. Karyotype was abnormal in seven of the 40 (17.5%) cases in which it was available., Conclusions: In a significant proportion of cases, most of the indirect signs of ACC are either absent or barely visible at the time of the midtrimester screening ultrasound examination. Therefore, ACC may escape diagnosis at midtrimester screening ultrasound. In particular, a third of examinations in fetuses with pACC may not show any abnormality in the transventricular screening view < 24 weeks. The medicolegal implications of such findings are important and should be considered., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Colpocephaly is a congenital abnormality in the ventricular system of the brain. The radiological diagnosis is usually made in the perinatal period and later presages intellectual disability. Adult cases of newly diagnosed colpocephaly have only rarely been reported. We have studied an adult with massive colpocephaly who is an otherwise functional woman. The diagnosis should be considered in patients with ventriculomegaly disproportionately affecting the occipital horns and must be differentiated from the more common form of adult ventriculomegaly-idiopathic normal pressure hydrocephalus (NPH).

Background and Purpose: Periventricular nodular heterotopia are common malformations of cortical development that are associated with many clinical syndromes and with many different neuroimaging phenotypes. The purpose of this study was to determine whether specific malformation phenotypes may be related to location, side, or number of PNH as assessed by MR imaging., Materials and Methods: MR images of 200 patients previously diagnosed with PNH were retrospectively analyzed. PNH were classified according to their location along the ventricles (anterior, posterior, or diffuse), side (unilateral or bilateral), and number of nodules (<5, 6-10, or >10). The cerebrum, brain stem and cerebellum were analyzed to assess associated anomalies. Associations between PNH location and the presence of other anomalies were tested by using Fisher exact test and χ2 test., Results: Posterior PNH were significantly associated with malformations of the cerebral cortex, diminished white matter volume, and mid-/hindbrain anomalies. Diffuse PNH were associated with diminished white matter volume, callosal "anomalies," and the presence of megacisterna magna. Unilateral PNH were strongly associated with cortical malformations., Conclusions: Certain malformation complexes are associated with PNH in specific locations: posterior PNH with cerebral cortical and mid-/hindbrain malformations and diffuse PNH with callosal anomalies and megacisterna magna. Knowledge of these associations should allow more directed analyses of brain MR imaging in patients with PNH. In addition, knowledge of these associations may help to direct studies to elucidate the causes of these malformation complexes.

Background and Purpose: Bilateral posterior PNH is a distinctive complex malformation with imaging features distinguishing it from classic bilateral PNH associated with FLNA mutations. The purpose of this study was to define the imaging features of posterior bilateral periventricular nodular heterotopia and to determine whether associated brain malformations suggest specific subcategories., Materials and Methods: We identified a cohort of 50 patients (31 females; mean age, 13 years) with bilateral posterior PNH and systematically reviewed and documented associated MR imaging abnormalities. Patients were negative for mutations of FLNA., Results: Nodules were often noncontiguous (n = 28) and asymmetric (n = 31). All except 1 patient showed associated developmental brain abnormalities involving a spectrum of posterior structures. A range of posterior fossa abnormalities affected the cerebellum, including cerebellar malformations and posterior fossa cysts (n = 38). Corpus callosum abnormalities (n = 40) ranged from mild dysplasia to agenesis. Posterior white matter volume was decreased (n = 22), and colpocephaly was frequent (n = 26). Most (n = 40) had associated cortical abnormalities ranging from minor to major (polymicrogyria), typically located in the cortex overlying the PNH. Abnormal Sylvian fissure morphology was common (n = 27), and hippocampal abnormalities were frequent (n = 37). Four family cases were identified-2 with concordant malformation patterns and 2 with discordant malformation patterns., Conclusions: The associations of bilateral posterior PNH encompass a range of abnormalities involving brain structures inferior to the Sylvian fissures. We were unable to identify specific subgroups and therefore conceptualize bilateral posterior PNH as a continuum of infrasylvian malformations involving the posterior cerebral and hindbrain structures.

Objective: To examine the possible association between aneuploidies and fetal lateral cerebral ventriculomegaly in the first trimester of pregnancy., Methods: Three-dimensional brain volumes were acquired by transvaginal ultrasound examination at 11-13 weeks' gestation in 410 euploid fetuses and 63 fetuses with trisomy 21, 34 with trisomy 18 and seven with trisomy 13. Lateral ventricles were assessed in a transverse view, just above the roof of the third ventricle and measurements of the areas of the lateral ventricles and choroid plexuses were obtained. The ratio between choroid plexus and lateral ventricle areas (CLR) was calculated. Measurements in aneuploid fetuses were compared to those in euploid fetuses., Results: In euploid fetuses the lateral ventricle and choroid plexus areas increased, whereas the CLR decreased with fetal biparietal diameter. In fetuses with trisomy 21, lateral ventricle and choroid plexus areas were smaller but CLR was not significantly different from that in euploid fetuses. In trisomy 18 and 13 fetuses, CLR was significantly smaller than in euploid fetuses. The CLR was below the 5(th) centile of normal range in 11 (32.4%) fetuses with trisomy 18 and in six (85.7%) with trisomy 13., Conclusion: There is evidence of ventriculomegaly at 11-13 weeks' gestation in most fetuses with trisomy 13 and one third of fetuses with trisomy 18., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: To document the incidence, natural history and compare neurodevelopmental outcome of newborns with and without frontal horn cysts (FHC)., Study Design: This was a case-control study. Newborns with and without FHC were identified and matched for demographics and worst cranial ultrasound scan (CUS) findings. Neurodevelopmental outcome was assessed at 18 to 24 months., Result: A total of 30 FHC cases were identified from medical imaging database. Twenty-five cases occurred in preterm 32 weeks gestation with an incidence of 1% (25 of 2340). The diagnosis was made on the initial CUS in 28 cases. The cyst size and number varied from 1 to 18 mm and 1 to 6 respectively with no change noted on repeat CUS during hospital stay. Neurodevelopmental outcomes were not statistically significantly different between the groups., Conclusion: FHC are not uncommon in the newborn period. They appear to be benign with no impact on neurodevelopmental outcome. This information is vital for counseling parents of infants with FHC.

A 39-year-old woman presented with long-standing overt ventriculomegaly in adults (LOVA) manifesting as gradually worsening headache. Past history included treatment for myeloschisis at birth. Intelligence quotient (IQ) was 115 and preoperative psychological assessment using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) showed normal scores in all domains. However, scores for constructional ability were slightly low. Computed tomography revealed severe ventriculomegaly involving the lateral and third ventricles, and magnetic resonance imaging showed aqueductal stenosis. Endoscopic third ventriculostomy was performed under a diagnosis of LOVA. Postoperatively, the headache resolved and the RBANS showed improvements in memory and constructional ability. Detailed evaluation of cognitive function provides a good indicator in the treatment of hydrocephalus with normal IQ.

Primary cilia are important sites of signal transduction involved in a wide range of developmental and postnatal functions. Proteolytic processing of the transcription factor Gli3, for example, occurs in primary cilia, and defects in intraflagellar transport (IFT), which is crucial for the maintenance of primary cilia, can lead to severe developmental defects and diseases. Here we report an essential role of primary cilia in forebrain development. Uncovered by N-ethyl-N-nitrosourea-mutagenesis, cobblestone is a hypomorphic allele of the IFT gene Ift88, in which Ift88 mRNA and protein levels are reduced by 70-80%. cobblestone mutants are distinguished by subpial heterotopias in the forebrain. Mutants show both severe defects in the formation of dorsomedial telencephalic structures, such as the choroid plexus, cortical hem and hippocampus, and also a relaxation of both dorsal-ventral and rostral-caudal compartmental boundaries. These defects phenocopy many of the abnormalities seen in the Gli3 mutant forebrain, and we show that Gli3 proteolytic processing is reduced, leading to an accumulation of the full-length activator isoform. In addition, we observe an upregulation of canonical Wnt signaling in the neocortex and in the caudal forebrain. Interestingly, the ultrastructure and morphology of ventricular cilia in the cobblestone mutants remains intact. Together, these results indicate a critical role for ciliary function in the developing forebrain.

Neuregulin-1 (Nrg1)/erbB signaling regulates neuronal development, migration, myelination, and synaptic maintenance. The Nrg1 gene is a schizophrenia susceptibility gene. To understand the contribution of Nrg1 signaling to adult brain structure and behaviors, we studied the regulation of type III Nrg1 expression and evaluated the effect of decreased expression of the type III Nrg1 isoforms. Type III Nrg1 is transcribed by a promoter distinct from those for other Nrg1 isoforms and, in the adult brain, is expressed in the medial prefrontal cortex, ventral hippocampus, and ventral subiculum, regions involved in the regulation of sensorimotor gating and short-term memory. Adult heterozygous mutant mice with a targeted disruption for type III Nrg1 (Nrg1(tm1.1Lwr+/-)) have enlarged lateral ventricles and decreased dendritic spine density on subicular pyramidal neurons. Magnetic resonance imaging of type III Nrg1 heterozygous mice revealed hypofunction in the medial prefrontal cortex and the hippocampal CA1 and subiculum regions. Type III Nrg1 heterozygous mice also have impaired performance on delayed alternation memory tasks, and deficits in prepulse inhibition (PPI). Chronic nicotine treatment eliminated differences in PPI between type III Nrg1 heterozygous mice and their wild-type littermates. Our findings demonstrate a role of type III Nrg1 signaling in the maintenance of corticostriatal components and in the neural circuits involved in sensorimotor gating and short-term memory.

Background and Purpose: Most previous neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) rely on the manual delineation of the region of interest, which is subjective and lacks reproducibility. The purpose of this study was to use an automated method to assess whether there are abnormalities in the brains of patients with ADHD. In view of findings from previous imaging and neuropsychologic studies, we predicted that we would detect abnormalities in many brain regions of patients with ADHD., Materials and Methods: Twelve boys with ADHD and 12 control subjects underwent MR imaging assessments. Statistically significant changes in regional volume were analyzed by using deformation based morphometry (DBM). This technique derived a voxel-wise estimation of regional tissue volume change from the deformation field required to warp subject to the template image. Morphologic differences between groups were estimated at each voxel, applying a threshold (P < .001) to the resulting voxel statistic maps to generate clusters of spatially contiguous suprathreshold voxels,, Results: The statistical results reveal some pronounced volume alterations in the brains of ADHD. Volume reductions are mainly localized in right prefrontal (Talairach 48, 20, 31), right medial temporal (Talairach 59, -52, 13), left parietal lobe (Talairach -32, -61, 41), and right basal ganglia (especially right putamen) (Talairach 21, 1, 11); the regions of volume enlargement in the brains of ADHD are observed in the right occipital lobe (Talairach 20, -86, 29) and in the left posterior lateral ventricle (Talairach -23, -40, 15)., Conclusion: Our findings confirm that there are widespread abnormalities in volume of boys with ADHD.

The present cadaveric study, describes asymmetrical right cerebral hemisphere and anomalous posterior horn of the right lateral ventricle and discusses its clinical implications. The occipital lobe of right cerebral hemisphere extended more posteriorly as compared to the left and so did the posterior horn of the lateral ventricle, resulting in the thinning of the occipital cortex. Till now, the dimension and volumetric study of the lateral ventricles have been usually performed by MRI and CT scans. A gross anatomical study of such a case, is the rarest of its kind. The abnormal anatomy of the lateral ventricles may be of great academic interest regarding CSF circulation and also important for clinical, radiological and surgical interventions (Fig. 2, Ref 8). Full Text (Free, PDF) www.bmj.sk.

Purpose: Mental retardation, facial dysmorphisms, and neurologic and brain abnormalities are features of 6q terminal deletions. Epilepsy is frequently associated with this chromosome abnormality, but electroclinical findings are not well delineated. We report five unrelated patients with 6q terminal deletions and a peculiar clinical, EEG, and neuroradiologic picture of epilepsy, mental retardation, and colpocephaly., Methods: These three male and two female patients underwent general and neurologic examinations, repeated awake and sleep EEGs, and brain magnetic resonance imaging (MRI). A cytogenetic study and fluorescent in situ hybridization (FISH) with chromosome-specific subtelomeric probes were carried out in all cases., Results: All subjects had seizures characterized by vomiting, cyanosis, and head and eye version, with and without loss of consciousness. In four cases, EEGs showed posterior spike-and-wave complexes, which were activated by sleep. No patient had status epilepticus or prolonged seizures. Brain MRI revealed colpocephaly and dysgenesis of the corpus callosum and brainstem in four patients; three of them also had hypertrophic massa intermedia. FISH analysis revealed a 6q terminal deletion in all patients, which ranged between 9 Mb (cases 2 and 3) and 16 Mb (case 4)., Conclusions: We suggest that epilepsy associated with 6q terminal deletions is a new entity. Patients with dysmorphic features associated with focal occipital epilepsy, colpocephaly, and dysgenesis of the corpus callosum, thalami, and brainstem should be considered candidates for testing for 6q subtelomere deletions.

To compare the linear dimensions (width) of the foetal atrium and occipital horns to their areas, 31 foetuses (15-24 weeks, C-R 12.5-23.5 mm) from spontaneous abortions were evaluated. Images of the axial sections of the brains were transferred to computer and Scion for Windows 98 software was used for image analysis. 11 brains appeared normal and 20 were abnormal (leukomalacia in 9 cases, periventricular and intraventricular haemorrhage in 6 cases, ventriculomegaly in 3 cases, colpocephaly in 1 case, vascular malformation in 1 case). High-range linear and planar asymmetries in the atrium and occipital horns were observed both in normal and abnormal brains. There was no close correlation between the width and the area of the structures under investigation, although it was stronger in case of the occipital horns. The wider occipital horns and atria often had a smaller area than the narrower ones. Some abnormal cerebral hemispheres had relatively narrow atria and occipital horns in comparison with their large areas. Further investigation should be carried out to assess the utility and potential superiority of planar measurements over linear in the image diagnosis of foetal ventricles.

We report here the characterization of a mutant mouse line with a specific gene trap event in the Mdm4 locus. Absence of Mdm4 expression results in embryonic lethality (10.5 days postcoitum [dpc]), which was rescued by transferring the Mdm4 mutation into a Trp53-null background. Mutant embryos were characterized by overall growth deficiency, anemia, improper neural tube closure, and dilation of lateral ventricles. In situ analysis demonstrated increased levels of p21(CIP1/Waf1) and lower levels of Cyclin E and proliferating cell nuclear antigen expression. Consistent with lack of 5-bromo-2'-deoxyuridine incorporation, these data suggest a block of mutant embryo cells in the G(1) phase of the cell cycle. Accordingly, Mdm4-deficient mouse embryonic fibroblasts manifested a greatly reduced proliferative capacity in culture. Moreover, extensive p53-dependent cell death was specifically detected in the developing central nervous system of the Mdm4 mutant embryos. These findings unambiguously assign a critical role for Mdm4 as a negative regulator of p53 and suggest that Mdm4 could contribute to neoplasias retaining wild-type Trp53. Finally, we provide evidence indicating that Mdm4 plays no role on cell proliferation or cell cycle control that is distinct from its ability to modulate p53 function.

Objective: To assess the clinical significance of fetal isolated borderline cerebral lateral ventriculomegaly defined as a width of the atrium of the lateral cerebral ventricles of 10-15 mm in the absence of other sonographically demonstrable malformations., Design: Retrospective study of the outcome of fetuses with a sonographic diagnosis of isolated borderline cerebral lateral ventriculomegaly and review of the English-language literature., Results: Of 31 fetuses, two had chromosomal aberrations (trisomy 21 and trisomy 13) and three had neurological complications (one infant developed shunt-dependent hydrocephalus, one lissencephaly and one cerebral hemorrhage and periventricular leukomalacia). The literature search revealed eight independent studies. Including the present series, 234 cases were available for analysis. An abnormal outcome was documented in 22.8% of cases. Perinatal death occurred in 3.7%. Chromosomal aberrations, mostly trisomy 21, were present in 3.8%, malformations undetected at a second-trimester sonogram in 8.6% and neurological sequelae, mostly a mild to moderate delay in cognitive and/or motor development, were present in 11.5%. The risk of an abnormal neurological outcome was increased in females versus males (22.6% versus 4.6%, relative risk 4.892; 95% confidence interval 1.356-17.656), when the atrial width was 12 mm or more (13.9% versus 3.8%, relative risk 3.6, 95% confidence interval 1.035-12.846) and when the diagnosis was made in the second trimester versus later in gestation., Conclusions: In most cases, isolated borderline cerebral lateral ventriculomegaly has no consequence. However, this finding carries an increased risk of cerebral maldevelopment, delayed neurological development and, possibly, chromosomal aberrations. The optimal management of these cases remains uncertain.

Objective: To report prospectively the prenatal diagnosis, management and outcome of 14 cases of unilateral ventriculomegaly., Methods: Fourteen fetuses were diagnosed as having one ventricle of > or = 10 mm, as measured at the level of the atrium., Results: In ten cases, the scan showed mild unilateral ventriculomegaly with an atrium width between 11 and 13 mm and this remained stable up to term. Eight of these fetuses had a magnetic resonance imaging scan in utero between 32 and 34 weeks of gestation which confirmed the diagnosis of mild ventriculomegaly without other brain abnormalities and showed a normal cortical mantle. No obvious cause was found and the outcome was normal in all cases. In four cases, the unilateral ventriculomegaly evolved rapidly with an atrium width up to 20-25 mm. Causes included atresia of the foramen of Monro, toxoplasmosis, brain atrophy and Weaver syndrome. Three underwent termination of pregnancy and the postmortem examination confirmed the diagnosis. The baby with brain atrophy and schizencephaly had a ventriculoperitoneal shunt placed at 1 month of age and has severe developmental delay at 9 months., Conclusion: The prognosis of unilateral ventriculomegaly is uncertain. Examination of both ventricles during the anomaly scan should be performed, as should ultrasound follow-up of these cases up to the end of the third trimester. Fetuses with an isolated, mild, stable unilateral ventriculomegaly seem to have a favourable neurological outcome. However, fetuses with rapidly evolving unilateral ventriculomegaly or cases associated with other brain abnormalities may have a poor neurological outcome.