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Dysgenesis of the corpus callosum is a rare developmental abnormality in brain structure that is associated with changes in physical appearance, as well as behavioral and cognitive consequences. A relatively commonly co-occurring structural abnormality with callosal dysgenesis is colpocephaly, characterized by enlargement of the posterior lateral ventricles and reductions in posterior brain volume. Although some case studies of individuals with this combination of structural malformations exist, they do not often report results of neuropsychological evaluation. Furthermore, those that do contain neuropsychological data may be of limited generalizability due to unique patient characteristics. The current manuscript overcomes these limitations by presenting the case of a 55-year-old male with callosal dysgenesis and colpocephaly identified in adulthood. The paper includes a full profile of his performance on a comprehensive neuropsychological test battery with discussion of differential diagnosis and treatment planning. Findings indicated low average intellectual abilities with deficits in processing speed, executive functions, and social cognition, consistent with expectations based on callosal dysgenesis. One surprising finding was that despite the significant posterior involvement of colpocephaly, visuospatial skills were a relative strength. The manuscript provides a clear characterization of callosal dysgenesis with colpocephaly to facilitate future clinical comparisons and set the stage for future research on this rare neuromorphological presentation.

Introduction: Ultrasound (US)-based indexes such as fronto-occipital ratio (FOR) can be used to obtain an acceptable estimation of ventricular volume. Patients with colpocephaly present a unique challenge due to the shape of their ventricles. In the present study, we aimed to evaluate the validity and reproducibility of the modified US-FOR index in children with Chiari II-related ventriculomegaly., Methods: In this retrospective study, we evaluated Chiari II patients younger than 1 year who underwent head US and MR or CT scans for ventriculomegaly evaluation. MR/CT-based FOR was measured in the axial plane by identifying the widest diameter of frontal horns, occipital horns, and the interparietal diameter (IPD). US-based FOR (US-FOR) was measured using the largest diameter based on the following landmarks: frontal horn and IPD in the coronal plane at the level of the foramen of Monro, IPD just superior to the Sylvian fissures, and occipital horn posterior to the thalami and inferior to the superior margins of the thalami. Intraclass correlation coefficients (ICCs) were used to evaluate inter-rater reliability, and Pearson correlation coefficients and Bland-Altman plots were applied to assess agreement between US and other two modalities., Results: Sixty-three paired US and MR/CT exams were assessed for agreement between US-FOR and MR/CT-FOR measurements. ICC showed an excellent inter-rater reliability for US-FOR (ICC = 0.99, p < 0.001) and MR/CT-FOR (ICC = 0.99, p < 0.001) measurements. The mean (range) values based on US-FOR showed a slight overestimation in comparison with MR/CT-FOR (0.51 [0.36-0.68] vs. 0.46 [0.34-0.64]). The Pearson correlation coefficient showed high cross-modality agreement for the FOR index (r = 0.83, p < 0.001). The Bland-Altman plot showed excellent concordance between US-FOR and MR/CT-FOR with a bias of 0.05 (95% CI: -0.03 to 0.13)., Conclusion: US-FOR in the coronal plane is a comparable tool for evaluating ventriculomegaly in Chiari II patients when compared with MR/CT-FOR, even in the context of colpocephaly., (© 2021 S. Karger AG, Basel.)

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.)

Colpocephaly is a form of congenital ventriculomegaly while porencephaly describes any full-thickness defect within the brain which usually presents as a cystic structure. Postulated aetologies include intrauterine/perinatal injuries, genetic disorders, and morphogenesis error. Colopocephaly and porencephaly is typically diagnosed in infancy while diagnosis in adulthood is exceptionally rare. We report a case of co-existence of colpocephaly with porencephaly diagnosed incidentally in a 54-year-old male presenting with subtle cognitive and neurologic abnormalities. Neuropsychological assessment revealed weaknesses in executive functions, processing speed, and language.To our knowledge, this is the only reported case of dual incidental findings of porencephaly and colpocephaly in an adult.

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.)

Purpose: The aim of our study was to assess the agreement between pre- and post-natal measurements in prenatal isolated ventriculomegaly., Methods: Ninety-two women were referred for lateral ventricular abnormality and followed prospectively. Cases with at least one dilated lateral ventricle ≥10 mm and a normal work up (serological tests, detailed anatomical scan, fetal brain MR imaging, genetic counseling, and amniocentesis) were considered idiopathic ventriculomegaly and comprised the study group for post-natal follow up. Prenatal measurements were performed by ultrasound and MR imaging. Post-natal measurements were performed by cranial sonography at age of 1-3 months. Measurements were performed in the customary plane for each modality. Paired Student's t test was used to assess the mean difference between pre- and postnatal measurements., Results: Forty three cases comprised the study group for post-natal measurements. A statistically significant decrease in ventricular width (p < .001) was observed between pre- and post-natal measurements. On clinical follow up for 24 months, all cases were normal except three who demonstrated very mild neurological deficits., Conclusions: Our study indicates statistically significant regression of prenatal isolated ventriculomegaly in the post-natal period.

Objective: To evaluate the clinical outcome of fetus diagnosed as mild and moderate isolated ventriculomegaly (IVM) and its correlation with imaging follow-up. Methods: Totally, 161 cases of single pregnancy whose fetus was diagnosed as mild or moderate IVM by ultrasound were administrated. Data of prenatal ultrasound examination, pregnancy outcomes, and the postnatal MRI results were collected. New borns' growth and development, language expression, movement coordination, auditory and visual function were followed up to evaluate the neurodevelopment. Results: (1) Before birth: 80.1% (129/161) of IVM disappeared before the delivery, 16.1% (26/161) remained stable, and 3.7% (6/161) continued to deteriorate. (2) Postnatal MRI: 8 cases (9.6%, 8/83) were diagnosed IVM, of which 3 cases were found additional abnormalities (1 case was the corpus callosum dysplasia and 2 cases were leukodystrophy) . The additional abnormal detection rate was 3/8. (3) Postnatal assessments: There were 7 cases (8.9%, 7/79) neunatal behavioral neurological assessment (NBNA) , 6 cases (7.6%, 6/79) Bayley scales of infant development (BSID) -psychomotor developmental index (PDI) and 3 cases (3.8%, 3/79) BSID-mental development index (MDI) whose scores were low. There was no significant difference of the NBNA and BSID scores between mild and moderate IVM (NBNA: χ(2)=2.042, P= 0.210; BSID-PDI: χ(2)=-1.359, P= 0.174; BSID-MDI: χ(2)=-1.205, P= 0.228) . Follow-up of 9 cases (11.4%, 9/79) with low BSID score, 6 of them were found to be stable in the medial ventricle of the uterus, and the size of the lateral ventricle was normal after birth by ultrasound and MRI. Conclusions: The majority of IVM fetuses have good prognosis, but there is also a risk of neurodevelopmental dysplasia. The postnatal follow-up should be paid attention to, and MRI should be performed as the postnatal imaging evaluation.

Objective: Isolated agenesis of the corpus callosum on fetal ultrasound has a varied prognosis. Microarray and exome sequencing (ES) might aid in prenatal counseling., Method: This study includes 25 fetuses with apparently isolated complete corpus callosum (cACC) on ultrasound. All cases were offered single nucleotide polymorphism array. Complementary ES was offered postnatally in selected cases. Clinical physical and neurodevelopmental follow-up was collected., Results: Eighteen cases opted for single nucleotide polymorphism array testing, which detected a causal anomaly in 2/18 (11.1%; 95% CI 2.0%-31%). Among ongoing pregnancies without a causal anomaly on microarray, 30% (95% CI 8.5%-60%) showed intellectual disability. Postnatal magnetic resonance imaging and physical examination often (64%; 95% CI 38%-85%, and 64%; 95% CI 38%-85%, respectively) revealed additional physical anomalies in cases without a causal anomaly on microarray. Two cases appeared truly isolated after birth. Postnatal sequencing in 4 of 16 cases without a causal anomaly on microarray but with intellectual disability and/or additional postnatal physical anomalies revealed 2 single-gene disorders. Therefore, the estimated diagnostic yield of ES in chromosomally normal cACC fetuses is between 2/4 (50%; 95% CI 11%-89%) and 2/16 (13.3%; 95% CI 2.4%-36%)., Conclusion: In accordance with current guidelines, we conclude that microarray should be offered in case of isolated cACC on ultrasound. ES is likely to be informative for prenatal counseling and should be offered if microarray is normal., (© 2017 John Wiley & Sons, Ltd.)

Objective: To explore the value of prenatal MRI in the diagnosis of fetal simple expansion of lateral ventricle (ventriculomegaly) , and follow up the nervous system development status after birth. Methods: Simple expansion of the lateral ventricle fetus by prenatal MRI examination were collected in Huzhou Maternal and Child Care Hospital from May 2013 to June 2015, 126 cases of live births in expansion group, 50 normal cases were recruited in the same period as the control group. In expansion group, fetal subgroup analysis was done: (1) unilateral or bilateral lateral ventricle expasion: one group was 98 cases was lateral ventricle expansion (77.8%, 98/126), expansion of bilateral ventricle group was 28 cases (22.2%, 28/126). (2) Prenatal MRI in the diagnosis of the lateral ventricle of expansion: expansion of the lateral ventricle width was greater than 10.0 mm, if both sides were expanding, the expand width was the heavier one side, divided into 3 subgroups: ①Expansion in group A (lateral ventricle width 10.0-12.0 mm) were 88 cases (69.8%, 88/126). ②Expansion in group B (lateral ventricle width 12.1-15.0 mm) were 29 cases (23.0%, 29/126). ③Expansion of group C (lateral ventricle width> 15.0 mm) were 9 cases (7.12%, 9/126). All 176 cases were followed up after birth at the 3rd, 6th, 12th, 18th month (corrected age was used for premature babies), and Gesell developmental schedules (GDS) were used to evaluate the neurobehavioral development. Results: (1) The MRI results after birth: 21 cases were followed up by MRI after birth. In group A, 11 cases had MRI and 9 were normal (the ventricular width <10.0 mm after birth), the other 2 cases were stable (the ventricular width measured first time after birth was ≥10.0 mm, but the difference was within 2.0 mm from the MRI before birth). In group B, 4 cases had MRI, 1 was normal, 1 was stable, and 2 cases were getting better (the ventricular width measured first time after birth was ≥10.0 mm, but the width decreased more than 2.0 mm from the MRI before birth). In group C, 6 cases had MRI. 3 cases were getting better and 3 cases were stable. (2) Overall GDS results: expansion group after the birth of the 3rd, 6th, 12th, 18th month GDS evaluation results compared with control group, respectively, the differences were not statistically significant (all P> 0.05). (3) The GDS results among the subgroups: in each evaluation after birth, there were no statistically significant differences between group A and the control group (all P> 0.05). The GDS results of group B at the 3rd and 6th month were lower than those of the control group ( P< 0.05); while there were no statistically significant differences between the 2 goups at the 12th and 18th month ( P> 0.05). And for group C, statistically significant differences were found compared to the control group at each follow-up time (all P< 0.05). (4) GDS results at different times after birth in the expansion group: there was no statistically significant difference between the results at the 3rd and 6th month ( P> 0.05). But when the result at the 3rd month was compared to the results of the 12th or 18th month, the differences were statistically significant ( P< 0.05). GDS result of 6th months after birth compared with 12th and 18th months, respectively, there were no statistically significant differences ( P> 0.05). There was no statistically significant difference between the results at the 12th and 18th month ( P> 0.05). (5) The GDS results in unilateral and bilateral ventricle expansion: at the 18th month, among the 98 unilateral cases, 86 (87.8%, 86/98) had normal GDS results( > 85 scores); 8 (8.2%, 8/98) had borderline results (75-85 scores); 4 (4.1%, 4/98) had delayed results ( < 75 scores). Among the 28 bilateral cases, 23 (82.1%, 23/28) had normal GDS results; 3 (10.7%, 3/28) had borderline results; 2 (7.1%, 2/28) had delayed results. There was no statistically significant difference ( P> 0.05). Conclusions: Among the simple expansion of lateral ventricle, those whose ventricular width are ≤12.0 mm may not need clinical treatment. If the width is between 12.1 to 15.0 mm, closely follow-up and targeted rehabilitation training after birth are recommended. When the width is more than 15.0 mm, the risk of the central nervous system function delay is significantly increased, and early intervention might improve the prognosis.

Fetal ventriculomegaly development leads to neurological, motor, and/or cognitive impairment, and is presently diagnosed based on the width of the atrium in the lateral ventricle. But in this study, we have tried to assess the relationship between the development of calcarine sulcus and width of fetal lateral ventricles, to assess if calcarine sulcus can also be used for fetal ventriculomegaly diagnosis. We conducted a retrospective analysis of the magnetic resonance imaging (MRI) data from 45 subjects with isolated mild fetal ventriculomegaly (IMVM). The calcarine sulcus development was divided into three categories based on the depth; Grade 1 (undeveloped), Grade 2 (underdeveloped), and Grade 3 (fully developed), and its correlation with fetal ventriculomegaly was analyzed based on Spearman's partial rank correlation test. Based on this analysis, the width of left and right lateral ventricles showed significant downward trend with the calcarine sulcus maturation [undeveloped (Left 13.88 ± 2.70 mm, Right 14.27 ± 3.13 mm) → underdeveloped (Left 12.95 ± 1.93 mm, Right 11.93 ± 2.24 mm) → fully developed (Left 11.06 ± 2.10 mm, Right 10.42 ± 2.10 mm)] (F Left  = 5.12, P = 0.01; F Right  = 10.72, P = 1.73 × 10 -4 ). In addition, significant correlations were also observed between the width of the lateral ventricles and the maturity of the calcarine sulcus (Spearman's rank correlation coefficient; -0.47 for the left lateral ventricles and -0.56 for the right, both P < 0.001). Overall, our data indicated a negative correlation between the fetal morphological development of calcarine sulcus and the width of lateral ventricles in subjects having isolated fetal ventriculomegaly., (© 2016 Japanese Teratology Society.)

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.

Objective: To investigate the relationship between fetal lateral ventriculomegaly and chromosomal microarray analysis (CMA) abnormalities., Methods: Fifty fetuses with lateral ventriculomegaly detected by ultrasound and a normal karyotype were included. Forty four fetuses were classified as mild ventriculomegaly (MVM), in which the lateral ventricular atrium was 10-15 mm. Six had severe ventriculomegaly (SVM), with the lateral ventricularatrium being ≥ 15 mm. The fetuses were also divided into isolated (n= 21) and non-isolated groups (n= 29) based on whether they are associated with other anomalies., Results: Thirteen (26%) of the fetuses were found to be abnormal by CMA. For the 44 cases with MVM, 9 (20.9% ) were found to be abnormal, while for the 6 cases with SMV, 4 (66.7%) were found to be abnormal (P>0.05). CMA abnormalities were found in 2 (9.5%) of the 21 fetuses with isolated ventriculomegaly group and 11 (37.9%) of the 29 fetuses with non-isolated ventriculomegaly group (P<0.05)., Conclusion: Chromosome microdeletions and microduplications are the most common abnormalities found in fetal lateral ventriculomegaly. When ventriculomegaly is associated with other anomalies, the incidence of CMA abnormally is much higher. Prenatal diagnosis is necessary for fetuses with lateral ventriculomegaly.

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.

Colpocephaly is a rare abnormality of the brain, described as persistence of primitive foetal configuration of lateral ventricles. It has been found in association with several abnormalities of the brain. Herein we report a case of colpocephaly with absent corpus callosum, confirmed antenatally with foetal MRI following diagnostic suspicion based on absent septum pellucidum at prenatal sonography., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

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.

Delleman syndrome (oculocerebrocutaneous syndrome, MIM 164180) is characterized by orbital cysts, microphthalmia/anophthalmia, focal skin defects, skin appendages and multiple cerebral malformations. We herein describe a case of an 8-month-old male child with features suggestive of Delleman syndrome along with a rare congenital lid anomaly - an accessory palpebral aperture, not reported so far to the best of our knowledge.

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.)

Background: Osteoporosis is a chronic disease characterized by bone loss and increased skeletal fragility. Large animal models are required for preclinical testing of new therapeutic approaches. We have recently demonstrated that continuous intracerebroventricular (ICV) application of leptin into the lateral ventricle (LV) induces bone loss in ewe. On the basis of these findings, we reasoned that the third ventricle (TV) is an even better target because of its closer location to the hypothalamus that mediates leptin effects on bone., Methods: Corriedale sheep were randomly mixed to four groups of four ewe each: control entire (control), ovarectomy plus ICV application of cerebrospinal fluid (OVX), OVX plus ICV application of leptin into the LV (leptin-LV); and ICV application of leptin into the TV (leptin-TV). After 3 months, histomorphometric characterization and bone turnover parameters were analyzed., Results: Highly significant loss of trabecular bone was observed only in leptin-LV group. Increased osteoclast indices and urinary cross-lap excretion were observed in OVX and leptin-TV group. In contrast, serum parameters of osteoblast activity were only significantly decreased in leptin-LV group. Autopsy of ewe brain showed fibrosis around the stainless steel cannula in leptin-TV group., Conclusions: ICV application of leptin into the LV strongly reduces bone formation and leads to a highly significant trabecular bone loss in ewe. In contrast, ICV application of leptin into the TV is technically more demanding and results are unpredictable, because the required use of stainless steel cannula induces peri-implant fibrosis that might prevent leptin to enter the cerebrospinal fluid.

Agenesis of the corpus callosum is associated with a wide range of neuropsychiatric symptoms. Cranial MRI confirms the diagnosis. We report a case of a 13-year-old boy with global developmental delay, mental retardation as well as neurological and psychiatric symptoms but without symptoms of ADHD who is unable to cope with school demands. Agenesis of the corpus callosum is a relatively rare, but possibly underestimated differential diagnosis of unclear retardations in development in children or suspicion of ADHD respectively.

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.

Objective: Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia., Method: Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts., Results: Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties., Conclusions: Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors' knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia.

Cystic malformations in the posterior cranial fossa result from developmental failure in the paleocerebellum and meninges. The authors present the case of an infant with hydrocephalus associated with cystic dilation of the foramina of Magendie and Luschka. This 7-month-old female infant presented with sudden onset of tonic-clonic seizures. Computed tomography revealed tetraventricular hydrocephalus. Magnetic resonance imaging demonstrated a cyst communicating with the fourth ventricle and projecting to the cisterna magna and the cerebellopontine cisterns through the foramina of Magendie and Luschka. A suboccipital craniotomy was performed for removal of the cyst wall, and the transparent membrane covering the foramen of Magendie was removed under a microscope. After the surgery, the patient's hydrocephalus improved and a phase contrast cine MR imaging study showed evidence of normal CSF flow at the level of the third and fourth ventricles. Three weeks later, however, the hydrocephalus recurred. An endoscopic third ventriculocisternostomy was performed to address the possibility of stagnant CSF flow in the posterior cranial fossa, but the hydrocephalus continued. Finally the patient underwent placement of a ventriculoperitoneal shunt, resulting in improvement of her symptoms and resolution of the hydrocephalus. On the basis of this experience and previously published reports, the authors speculate that the cystic malformation in their patient could be classified in a continuum of persistent Blake pouch cysts. Hydrocephalus was caused by a combination of obstruction of CSF flow at the outlets of the fourth ventricle and disequilibrium between CSF production and absorption capacity.

Pathological-anatomical autopsy is the gold standard for determining of foetal abnormalities, but in some cases its role is limited (pathology of central nervous system, in particular, in case of ventricular dilatation or developed autolysis). In pathology of central nervous system, where insufficiency of autopsy can occur, additional post mortem magnetic resonance imaging (MRI) is performed to determine type of malformation. In this case report, we would like to point out the fact that although all investigating methods including post mortem magnetic resonance and autopsy (incl. imunohistochemical tests) are used, this need not necessarily result in a clear diagnostic conclusion of the aborted foetus. Post mortem MRI visualized pathology: dilatation of both lateral ventricals, more in the left and, above all, a pathological focus parasagittaly on the right with haemorrhage and cystic component; it raised a suspicion on ependymoma. However imunohistochemical test did not give an unambiguous conclusion; therefore diagnosis based on MRI could not be uniquely verified.

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.

MRI appearance of Sturge-Weber Syndrome (SWS) in patients with Tuberous Sclerosis (TSC) has been rarely reported. We describe a new patient with confirmed diagnosis of TSC and MRI appearance of SWS and review the pertinent literature. We discuss these findings on the basis of the new classifications of brain malformations, which take into account the role of neural-crest. The coexistence of signs of both diseases in the same individuals could be explained by common altered pathways that could lead to an anomalous angiogenesis.

Aim: The aim of this study was to evaluate the clinical significance and the management of fetal borderline lateral cerebral ventriculomegaly., Methods: Fetuses with a sonographic diagnosis of lateral cerebral ventriculomegaly isolated or associated to other fetal malformations were followed monthly and a review of the English-language literature was made., Results: Of 86 fetuses analyzed, 30 suffered from hydrocephaly (monolateral, bilateral), 56 showed also several other malformations . Chromosomal aberrations is possible also in case of isolated hydrocephaly. Neurological sequelae, mostly a mild to moderate delay in cognitive and/or motor development, is present in 10% of the cases., Conclusions: In most cases, isolated borderline lateral cerebral ventriculomegaly has no consequence. However, the risk of cerebral maldevelopment, delayed neurological development and, possibly, chromosomal aberrations is increased. The optimum management of these cases remains uncertain.

Ventriculomegaly at term age is an important predictor of neurologic outcome in preterm infants. Previous studies have found only poor correlations between two-dimensional (2D) cranial ultrasound (US) measurements of lateral ventricles and volume measurements using three-dimensional (3D) magnetic resonance imaging (MRI). Paired cranial MRI and US scans in a population based cohort of 28 extremely preterm infants were obtained at term equivalent age. A 3D MRI volume and five different 2D ultrasound measurements were assessed for each lateral ventricle. Correlations and interobserver variability were calculated. Reliability of US measurements and correlations between MRI volumes and US measurements of the frontal horns and ventricular midbody were consistently good. The highest correlation was achieved by combining the coronal frontal horn measurements to a frontal horn product (r(2) = right 0.94, left 0.95). Our study underlines the value of cranial ultrasound measurements in neonatal care and follow-up.

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.

Purpose: The purpose of this study was to evaluate the association of asymmetric lateral ventricle (ALV) with clinical and structural pathologies and assess its clinical importance., Materials and Methods: We analyzed 170 consecutive ALV cases on computed tomography (CT) and 170 control group patients with normal head CT. Patients who had apparent etiologic causes for ALV were excluded. The differential diagnosis of ALV and unilateral hydrocephalus (UH) was made by using three different ventricle-brain ratios (VBRs). The measurements of the ALV were made at the frontal horn level. Patients with asymmetry were divided into three subgroups including mild, moderate and severe groups to eloborate the grade of the ventricular asymmetry. Additional CT findings including septal deviation, diffuse enlargement, atrophy and the densities of constant sites were also recorded systematically for each patient. Clinical and handedness data were collected and analyzed., Results: The prevalence of ALV in the study population was 6.1%. Headache was the most common reason for head CT examination and was significantly more common in the asymmetry group (61.7% in group A, 42.9% in group B, P = 0.001). Transient ischemic attack, focal neurologic findings, vertigo, ataxia, visual and hearing disturbances were similar in both groups (P > 0.5). There was no difference in smoking and alcohol habits in both patient groups. Ten (5.8%) patients in group A and 16 (9.4%) patients in group B had neuropsychiatric disorders, which did not achieve statistical significance. In group A patients, the larger ventricle was more common in the left side than in the right (left = 70.0%, right = 30.0%). Group A consisted of 57.0% mild (grade 1, n = 97), 26.5% moderate (grade II, n = 45) and 16.5% severe (grade III, n = 28) patients. There was no significant correlation between handedness and ALV. The density of different brain sites was found close similar on both sides in ALV and control group (P > 0.5). Choroidal cystic or solid neoplasm or periventricular dysplasia was detected in six ALV patients in group A (3.5%), on their additional MR examinations., Conclusion: The physician should not overlook an ALV finding on unenhanced CT, particularly in cases with severe degree of asymmetry or diffuse ventricular enlargement, and search for possible accompanying disorders.

Objective: To discuss the relationship between XYY chromosome abnormality, psychiatric disorders and epilepsy., Method: Single case report., Results: A 34-year-old man with 47, XYY karyotype and normal intelligence was followed-up at a neuropsychiatric clinic for over 30 years. He was first seen at age 3 years with a history of delayed motor and language development and an immunodeficiency syndrome. At age 8 years he developed refractory focal epilepsy, and in late adolescence he started to exhibit increasingly prominent obsessive thoughts, paranoid ideation, and aggressive sexual fantasies and behaviour., Conclusions: When interpreted within the context of previous literature reports, this case suggests a pathophysiological link between XYY chromosome abnormality, characteristic psychiatric symptoms and epilepsy disorder.

Schizencephaly is a rare anomaly of neuronal migration characterized by the presence of brain clefts that communicate with the lateral ventricles. Type I is characterized by clefts with fused lips or margins, not communicating with the subarachnoid space. Type II is characterized by longer clefts that communicate with the subarachnoid space. Neonatal diagnosis of schizencephaly on transfontanellar two-dimensional (2D) sonography is rare, with only 1 report in the medical literature. The major limitation of 2D sonography is its inability to assess neonatal prognosis. There are no reports on MEDLINE about the use of transfontanellar three-dimensional (3D) sonography in the assessment of schizencephaly. We present a case of type II schizencephaly diagnosed on the 29th week of gestation with 2D sonography and describe the main findings with 3D sonography in surface and transparency modes performed in the neonatal period via the fontanel., ((c) 2007 Wiley Periodicals, Inc.)

The rat ortholog of the WD40 repeat protein Wdr16 is abundantly expressed in testis and cultured ependymal cells. Low levels are found in lung and brain, respectively, while it is absent from kinocilia-free tissues. In testis and ependymal primary cultures, Wdr16 messenger RNA appears concomitantly with the messages for sperm-associated antigen 6, a kinocilia marker, and for hydin, a protein linked to ciliary function and hydrocephalus. In testis, ependyma and respiratory epithelium, the Wdr16 protein is up-regulated together with kinocilia formation. The wdr16 gene is restricted to genera in possession of kinocilia, and it is strongly conserved during evolution. The human and zebrafish proteins are identical in 62% of their aligned amino acids. On the message level, the zebrafish Wdr16 ortholog was found exclusively in kinocilia-bearing tissues by in situ hybridisation. Gene knockdown in zebrafish embryos by antisense morpholino injection resulted in severe hydrocephalus formation with unaltered ependymal morphology or ciliary beat. Wdr16 can be considered a differentiation marker of kinocilia-bearing cells. In the brain, it appears to be functionally related to water homeostasis or osmoregulation.