Validation of Sonographic Fronto-Occipital Ratio Based on Anatomical Landmarks Compared to MR/CT-Derived Indexes in Children with Chiari II and Ventriculomegaly.

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.

Comprehensive genetic analysis confers high diagnostic yield in 16 Japanese patients with corpus callosum anomalies.

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.

Neuropsychological presentation of colpocephaly and porencephaly with symptom onset in adulthood.

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.

[Analysis of the prognosis of isolated ventriculomegaly and outcome of imaging follow-up].

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.

Advanced genomic testing may aid in counseling of isolated agenesis of the corpus callosum on prenatal ultrasound.

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.

[Clinical value of prenatal MRI in the diagnosis of fetal simple expansion of lateral ventricle and follow-up after birth].

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.

Morphometric variability of neuroimaging features in children with agenesis of the corpus callosum.

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.

[Chromosomal microarray analysis for lateral ventriculomegaly in fetus].

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.

Prenatal diagnosis of colpocephaly with absent corpus callosum.

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.

Neurodevelopmental outcome in isolated mild fetal ventriculomegaly: systematic review and meta-analysis.

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.

Agenesis of the fetal corpus callosum: sonographic signs change with advancing gestational age.

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.

Lateral ventricles in fetuses with aneuploidies at 11-13 weeks' gestation.

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.

Neuropsychological functioning in dysgenesis of the corpus callosum with colpocephaly.

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.

[Agenesis of the corpus callosum: Cognitive and neuropsychiatric symptoms in children and adolescents--a case report]. / Balkenagenesie - Kognitive und neuropsychiatrische Symptome im Kindes- und Jugendalter.

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.

Is it always possible to determine a diagnosis? Prenatal ultrasonography, post mortem magnetic resonance, autopsy.

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 crucial role for primary cilia in cortical morphogenesis.

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.

Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit components.

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.