Corpus Callosum Abnormalities Research Articles

CANPMR Syndrome and Chromosome 1p32-p31 Deletion Syndrome Coexist in Two Related Individuals Affected by Simultaneous Haplo-insufficiency of CAMTA1 and NIFA Genes

Non-progressive cerebellar ataxia with mental retardation (CANPMR, OMIM 614756) and chromosome 1p32-p31 deletion syndrome (OMIM 613735) are two very rare inherited disorders, which are caused by mono-allelic deficiency (haplo-insufficiency) of calmodulin-binding transcription activator 1 (CAMTA1) and, respectively, nuclear factor 1 A (NFIA) genes. The yet reported patients affected by mono-allelic CAMTA1 dysfunction presented with neonatal hypotonia, delayed and ataxic gait, cerebellar atrophy, psychological delay and speech impairment, while individuals carrying a disrupted NFIA allele suffered from agenesis/hypoplasia of the corpus callosum, ventriculomegaly, developmental delay and urinary tract abnormalities. Both disorders were not seen in one patient together before. In this study two related individuals affected by a complex clinical syndrome, characterized by cognitive, neurological and nephrological features were studied for the underlying genetic disorder(s) by molecular cytogenetics. The two individuals present dysmorphic facies, macrocephaly, generalized ataxia, mild tremor, strabismus, mild mental retardation and kidney hypoplasia. Moreover, neuro-radiological studies showed hypoplasia of corpus callosum. Genetic investigations revealed a paracentric inversion in the short arm of one chromosome 1 with breakpoints within CAMTA1 and NFIA coding sequences. To the best of our knowledge, this is the first report of two patients harboring the simultaneous mono-allelic disruptions and consequent haplo-insufficiencies of two genes due to an inversion event. Disruption of CAMTA1 and NFIA genes led to neuro-psychological and nephrological dysfunctions, which comprised clinical features of CANPMR syndrome as well as chromosome 1p32-p31 deletion syndrome.

Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study

Objective To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika...

20. Cortical brain connectivity evaluated by graph theory in dementia: A correlation study between functional and structural data

Functional connectivity, revealed by EEG, evaluates time synchronization in anatomically distinct but functionally collaborating brain regions. Structural connection, revealed by diffusion tensor imaging (DTI), detects fractional anisotropy (FA). FA decreases in pathological aging corpus callosum (CC) and could reflect functional disconnections. We investigated correlations between structural damage of CC (MRI-DTI) and functional abnormalities of brain integration (cortical Characteristic Path Length of EEG). Resting state EEG and MRI were evaluated in 9 healthy controls-Nold, 10 Mild Cognitive Impairment – MCI, 10 mild Alzheimer Disease – AD, 11 moderate AD. Undirected and weighted brain network was built to evaluate graph Path Length weighting network edges by eLORETA lagged connectivity. Callosal FA reduction was associated to a loss of brain interhemispheric functional connectivity characterized by increased delta and decreased alpha Path Length. Global (path length as index of how efficient is the information transfer inside network) functional measure can reflect the reduction of fibers connecting the hemispheres as revealed by DTI. Functional and structural disconnections do not share the same timing (functional coming first) in the prodromal stage of disease, but in disease evolution (from healthy to dementia) it is possible to obtain statistical correlations between connectivity’s indexes.

Cochlear implantation in a child with subtelomeric 1q deletion syndrome and Dandy–Walker malformation

Abstract Subtelomeric 1q deletion syndrome is a rare disorder characterized by severe mental and growth retardation, microcephaly, distinct facial features and corpus callosum abnormalities. Senserineural hearing loss is not common in this syndrome. We report a 2-year-old boy with subtelomeric 1q deletion syndrome presented with typical craniofacial abnormalities and bilateral senserineural hearing loss. Imaging revealed corpus callosum hypogenesis and Dandy-Walker malformation. Cochlear implantation was successfully undertaken using a transmastoid facial recess aproach. After 12-months post-implantation, good audiological outcomes were obtained. Cochlear implantation can be considered for hearing rehabilitation in patients with subtelomeric 1q deletion syndrome and Dandy-Walker malformation.

Integrity of the corpus callosum in patients with benign temporal lobe epilepsy.

Corpus callosum (CC) abnormalities are frequently reported in patients with refractory mesial temporal lobe epilepsy (rMTLE). However, whether CC structural alterations are related to the epileptic syndrome itself or to refractoriness is still unknown. Thus, we aimed to compare patterns of CC change in patients with rMTLE and benign MTLE (bMTLE), the latter of which represents a useful resource to better disentangle factors that contribute to refractoriness. The study group included 79 patients with bMTLE (mean age 43.2 ± 14. 8 years), 61 with rMTLE (mean age 45.2 ± 12.4 years) and 134 healthy volunteers. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were performed to measure thickness, mean diffusivity (MD), and fractional anisotropy (FA) over 50 regions of interest along the cross-sectional CC profile. Statistical analysis comprised analysis of variance (ANOVA) followed by post hoc Tukey's Honest Significant Difference test. We found that all imaging metrics of the CC splenium were altered in rMTLE patients compared to bMTLE and controls. We also found significantly reduced thickness and FA of the anterior CC in rMTLE compared to controls and that FA was reduced only in rMTLE compared to bMTLE. Patients with bMTLE did not differ from controls. Differences between disease subgroups were found in the midbody composed of sensorimotor fibers. We found altered multimodal imaging metrics of the CC in rMTLE but not in bMTLE. These findings were independent of the radiologic presence of hippocampal sclerosis, suggesting that differences in the distribution of such alterations might be related to refractoriness.

Reinforcing the association between distal 1q CNVs and structural brain disorder: A case of a complex 1q43-q44 CNV and a review of the literature.

Copy Number Variations (CNVs) comprising the distal 1q region 1q43-q44 are associated with neurological impairments, structural brain disorder, and intellectual disability. Here, we report an extremely rare, de novo case of a 1q43-q44 deletion with an adjacent duplication, associated with severe seizures, microcephaly, agenesis of the corpus callosum, and pachygyria, a consequence of defective neuronal migration disorder. We conducted a literature survey to find that our patient is only the second case of such a 1q43-q44 CNV ever to be described. Our data support an association between 1q43-q44 deletions and microcephaly, as well as an association between 1q43-q44 duplications and macrocephaly. We compare and contrast our findings with previous studies reporting on critical 1q43-q44 regions and their constituent genes associated with seizures, microcephaly, and corpus callosum abnormalities [Ballif et al., 2012; Hum Genet 131:145-156; Nagamani et al., 2012; Eur J Hum Genet 20:176-179]. Taken together, our study reinforces the association between 1q43-q44 CNVs and brain disorder.

CANPMR syndrome and chromosome 1p32-p31 deletion syndrome coexist in two related individuals affected by simultaneous haplo-insufficiency of CAMTA1 and NFIA genes

BackgroundNon-progressive cerebellar ataxia with mental retardation (CANPMR, OMIM 614756) and chromosome 1p32-p31 deletion syndrome (OMIM 613735) are two very rare inherited disorders, which are caused by mono-allelic deficiency (haplo-insufficiency) of calmodulin-binding transcription activator 1 (CAMTA1) and, respectively, nuclear factor 1 A (NFIA) genes. The yet reported patients affected by mono-allelic CAMTA1 dysfunction presented with neonatal hypotonia, delayed and ataxic gait, cerebellar atrophy, psychological delay and speech impairment, while individuals carrying a disrupted NFIA allele suffered from agenesis/hypoplasia of the corpus callosum, ventriculomegaly, developmental delay and urinary tract abnormalities. Both disorders were not seen in one patient together before.ResultsIn this study two related individuals affected by a complex clinical syndrome, characterized by cognitive, neurological and nephrological features were studied for the underlying genetic disorder(s) by molecular cytogenetics. The two individuals present dysmorphic facies, macrocephaly, generalized ataxia, mild tremor, strabismus, mild mental retardation and kidney hypoplasia. Moreover, neuro-radiological studies showed hypoplasia of corpus callosum. Genetic investigations revealed a paracentric inversion in the short arm of one chromosome 1 with breakpoints within CAMTA1 and NFIA coding sequences.ConclusionsTo the best of our knowledge, this is the first report of two patients harboring the simultaneous mono-allelic disruptions and consequent haplo-insufficiencies of two genes due to an inversion event. Disruption of CAMTA1 and NFIA genes led to neuro-psychological and nephrological dysfunctions, which comprised clinical features of CANPMR syndrome as well as chromosome 1p32-p31 deletion syndrome.

EPILEPSY MANIFESTATIONS IN PATIENTS WITH MALFORMATIONS OF THE CORPUS CALLOSUM

The article deals with epileptic manifestations with malformations of the corpus callosum of the example of two disembriogenetic syndromes (Aicardi syndrome and Pierre-Robin syndrome). These hereditary syndromes have in common is expressed epileptic manifestations, malformations of the corpus callosum and other somatic congenital abnormality. The treatment is mainly symptomatic. Unlike most other neurogenetic syndromes with known molecular defect, DNA testing at Aicardi syndrome and Pierre-Robin syndrome is very difficult task, and the focus of the diagnosis of the disease belongs to the complex clinical and neuroimaging studies. Timely detection of these syndromes is a difficult task that requires a great deal of clinical experience, practical knowledge, not only in neuroscience but also in the related fields of medicine.

Enlarged lateral ventricles inversely correlate with reduced corpus callosum central volume in first episode schizophrenia: association with functional measures.

The lateral and third ventricles, as well as the corpus callosum (CC), are known to be affected in schizophrenia. Here we investigate whether abnormalities in the lateral ventricles (LVs), third ventricle, and corpus callosum are related to one another in first episode schizophrenia (FESZ), and whether such abnormalities show progression over time. Nineteen FESZ and 19 age- and handedness-matched controls were included in the study. MR images were acquired on a 3-Tesla MRI at baseline and ~1.2years later. FreeSurfer v.5.3 was employed for segmentation. Two-way or univariate ANCOVAs were used for statistical analysis, where the covariate was intracranial volume. Group and gender were included as between-subjects factors. Percent volume changes between baseline and follow-up were used to determine volume changes at follow-up. Bilateral LV and third ventricle volumes were significantly increased, while central CC volume was significantly decreased in patients compared to controls at baseline and at follow-up. In FESZ, the bilateral LV volume was also inversely correlated with volume of the central CC. This inverse correlation was not present in controls. In FESZ, an inverse correlation was found between percent volume increase from baseline to follow-up for bilateral LVs and lesser improvement in the Global Assessment of Functioning score. Significant correlations were observed for abnormalities of central CC, LVs and third ventricle volumes in FESZ, suggesting a common neurodevelopmental origin in schizophrenia. Enlargement of ventricles was associated with less improvement in global functioning over time.

Corpus callosum abnormalities: neuroradiological and clinical correlations.

To study neuroradiological features in pediatric patients with corpus callosum abnormalities, using new functional subtyping for the corpus callosum, and to correlate the features with the clinical presentation. We performed a retrospective review of 125 patients with radiologically identified abnormalities of the corpus callosum seen between 1999 and 2012. The study reviewed clinical features, genetic etiology, and chromosomal microarray (CMA) results. We used a new functional classification for callosal abnormalities based on embryological and anatomical correlations with four classes: complete agenesis, anterior agenesis (rostrum, genu, body), posterior agenesis (isthmus, splenium), and complete hypoplasia (thinning). We also studied the presence of extracallosal abnormalities. The new functional callosal subtyping did not reveal significant differences between the various subtypes in association with neurological outcome; however, the presence of cardiac disease was found more frequently in the group with complete agenesis. Thirty-seven per cent (46/125) had identifiable causes: of these, 48% (22/46) had a monogenic disorder, 30% (14/46) had a pathogenic chromosomal copy-number variant detected by CMA or karyotype, and 22% (10/46) had a recognizable clinical syndrome for which no confirmatory genetic test was available (namely Aicardi syndrome/septo-optic dysplasia and Goldenhar syndrome). The diagnostic yield for a significant CMA change was 19%. The presence of Probst bundles was found to be associated with a better neurodevelopmental outcome. The functional classification system alone 'without clinical data' cannot predict the functional outcome. The presence of extracallosal brain abnormalities and an underlying genetic diagnosis predicted a worse neurodevelopmental outcome. This study highlights the importance of CMA testing and cardiac evaluation as part of a routine screen.

REMOVED: Corpus callosum abnormalities in medication-naïve adult patients with obsessive compulsive disorder

This article has been removed: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our‐business/policies/article‐withdrawal)This meeting abstract has been removed by the Publisher. Due to an administrative error, abstracts that were not presented at the ISDN 2014 meeting were inadvertently published in the meeting's abstract supplement. The Publisher apologizes to the authors and readers for this error.

Detection of Fetal Corpus Callosum Abnormalities by Means of 3D Ultrasound.

The objective of this study was to prenatally detect corpus callosum pathologies such as agenesis, partial agenesis, hypo- and hyperplasia and enhanced echogenicity. Between 2009 and 2013 detailed 3D ultrasound examinations of the fetal corpus callosum were carried out as part of a level III examination for fetal anomalies. All scans were performed using Voluson E8 equipment (GE, Zipf, Austria) with a 5 - 8 MHz 3D transabdominal and 5 - 9 MHz 3D transvaginal transducer. All cases were evaluated for the following variables: inner, outer and curved length of the corpus callosum, height of the different segments of the corpus callosum and the corpus callosum area. All parameters were compared with normal growth charts. In all cases of suspected corpus callosum anomaly direct and indirect signs for corpus callosum agenesis and associated malformations were observed. 31 fetuses with pathological corpus callosum were diagnosed with 3D ultrasound. Gestational age at the time of diagnosis ranged from 20 to 38 weeks. 12 cases showed agenesis, 11 cases partial agenesis, 5 cases hypoplasia, 2 cases acombination of partial hyper- and hypoplasia and one case a lipoma of the corpus callosum. In corpus callosum underdevelopment, the more affected parts were the body and splenium. Associated anomalies were present in 25 of the 31 cases (80.6%) of corpus callosum pathologies. 3D neurosonography serves as an excellent tool to precisely demonstrate the pathological development of the fetal corpus callosum. By correlating the measures with the function of each affected corpus callosum segment, we can try to get a vague prediction of the neurological prognosis.

Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment.

Familial recurrences of FOXG1-related disorder: Evidence for mosaicism.

FOXG1-related disorders are caused by heterozygous mutations in FOXG1 and result in a spectrum of neurodevelopmental phenotypes including postnatal microcephaly, intellectual disability with absent speech, epilepsy, chorea, and corpus callosum abnormalities. The recurrence risk for de novo mutations in FOXG1-related disorders is assumed to be low. Here, we describe three unrelated sets of full siblings with mutations in FOXG1 (c.515_577del63, c.460dupG, and c.572T > G), representing familial recurrence of the disorder. In one family, we have documented maternal somatic mosaicism for the FOXG1 mutation, and all of the families presumably represent parental gonadal (or germline) mosaicism. To our knowledge, mosaicism has not been previously reported in FOXG1-related disorders. Therefore, this report provides evidence that germline mosaicism for FOXG1 mutations is a likely explanation for familial recurrence and should be considered during recurrence risk counseling for families of children with FOXG1-related disorders.

Accelerated corpus callosum development in prematurity predicts improved outcome.

To determine: (1) whether corpus callosum (CC) size and microstructure at 7 years of age or their change from infancy to 7 years differed between very preterm (VP) and full-term (FT) children; (2) perinatal predictors of CC size and microstructure at 7 years; and (3) associations between CC measures at 7 years or trajectories from infancy to 7 years and neurodevelopmental outcomes. One hundred and thirty-six VP (gestational age [GA] <30 weeks and/or birth weight <1,250 g) and 33 FT children had usable magnetic resonance images at 7 years of age, and of these, 76 VP and 16 FT infants had usable data at term equivalent age. The CC was traced and divided into six sub-regions. Fractional anisotropy, mean, axial, radial diffusivity and volume were measured from tractography. Perinatal data were collected, and neurodevelopmental tests administered at 7 years' corrected age. VP children had smaller posterior CC regions, higher diffusivity and lower fractional anisotropy compared with FT 7-year-olds. Reduction in diffusivity over time occurred faster in VP than FT children (P ≤ 0.002). Perinatal brain abnormality and earlier GA were associated with CC abnormalities. Microstructural abnormalities at 7 years or slower development of the CC were associated with motor dysfunction, poorer mathematics and visual perception. This study is the first to demonstrate an accelerated trajectory of CC white matter diffusion following VP birth, associated with improved neurodevelopmental functioning. Findings suggest there is a window of opportunity for neurorestorative intervention to improve outcomes. Hum Brain Mapp 36:3733-3748, 2015. © 2015 Wiley Periodicals, Inc.

Polymorphism within a Neuronal Activity-Dependent Enhancer of NgR1 Is Associated with Corpus Callosum Morphology in Humans

The human Nogo-66 receptor 1 (NgR1) gene, also termed Nogo receptor 1 or reticulon 4 receptor (RTN4R) and located within 22q11.2, inhibits axonal growth and synaptic plasticity. Patients with the 22q11.2 deletion syndrome show multiple changes in brain morphology, with corpus callosum (CC) abnormalities being among the most prominent and frequently reported. Thus, we hypothesized that, in humans, NgR1 may be involved in CC formation. We focused on rs701428, a single nucleotide polymorphism of NgR1, which is associated with schizophrenia. We investigated the effects of the rs701428 genotype on CC structure in 50 healthy participants using magnetic resonance imaging. Polymorphism of rs701428 was associated with CC structural variation in healthy participants; specifically, minor A allele carriers had larger whole CC volumes and lower radial diffusivity in the central CC region compared with major G allele homozygous participants. Furthermore, we showed that the NgR1 3′ region, which contains rs701428, is a neuronal activity-dependent enhancer, and that the minor A allele of rs701428 is susceptible to regulation of enhancer activity by MYBL2. Our results suggest that NgR1 can influence the macro- and microstructure of the white matter of the human brain.

Corpus Callosum Structure is Topographically Correlated with the Early Course of Cognition and Depression in Alzheimer's Disease.

Corpus callosum (CC) abnormalities may cause cognitive and neuropsychiatric complications due to reduced hemispheric integration. Over a one-year period, we investigated whether the CC structure of 20 patients with mild Alzheimer's disease (AD) was linked to the evolution of cognitive and neuropsychiatric symptoms. We also investigated whether this anatomical-clinical relationship was localized topographically on the CC by combining voxel-based morphometry and diffusion tensor imaging approaches. We assessed patients' global cognitive deterioration and neuropsychiatric symptoms with the Mini-Mental State Examination and the Neuropsychiatric Inventory. Increased global cognitive deterioration during the early course of AD was significantly related to reduced white matter density (p = 0.004) and fractional anisotropy (FA) (p = 0.012) and increased mean diffusivity (MD) (p = 0.017) at the level of the CC isthmus/splenium. Further, increased depression severity was significantly related to reduced FA (p = 0.008) and increased MD (p = 0.018) at the level of the CC rostrum. These results indicate that changes in early myelinated CC fibers, which subserve the lateral temporal and parietal cortices and are less vulnerable to damage, may be related to cognitive impairment. Furthermore, changes in late myelinated CC fibers, which connect the orbitofrontal cortices and are more vulnerable to damage, may be related to the earliest neuropsychiatric symptoms of AD, such as depression.

Children born to women treated for hypothyroidism during pregnancy show abnormal corpus callosum development.

Thyroid hormone (TH) is essential for the developing brain, and because the fetal thyroid develops relatively late in gestation, the maternal TH supply is critical for fetal brain development. However, if the mother has hypothyroidism during pregnancy, fetal brain and neuropsychological development may be compromised. Rodents experiencing maternal TH insufficiency show abnormal corpus callosum (CC) morphology, but it is not known if children born to women treated for hypothyroidism (HYPO) show similar effects. The purpose of the current study was to investigate HYPO for CC morphology and morphometry and to determine whether any specific CC abnormalities were associated aspects of maternal hypothyroidism and were correlated with reduced neuropsychological functioning in the children. ANALYZE software was used to trace CCs in archived magnetic resonance imaging scans from 22 HYPO and 22 matched controls. Areas of two sub-regions and six segments and different shape metrics (angles, lengths, ratios) were determined. CC parameters were correlated with maternal thyrotropin (TSH) values and number of hypothyroid trimesters as well as the child's neuropsychological test performance. HYPO showed a smaller anterior CC and genu and larger posterior CC and splenium areas than controls as well as shape abnormalities in genu and splenium. Results were correlated with the duration of maternal hypothyroidism. Executive function skills were positively associated with genu size in HYPO, while verbal comprehension skills were negatively associated with splenium and overall posterior CC sizes. Maternal hypothyroidism contributes to CC abnormalities in the offspring, and effects differ for anterior versus posterior CC regions.

Abnormality of the corpus callosum in coalmine gas explosion-related posttraumatic stress disorder.

Abnormal corpus callosum (CC) has been reported in childhood trauma-related posttraumatic stress disorder (PTSD); however, the nature of white matter (WM) integrity alterations in the CC of young adult-onset PTSD patients is unknown. In this study, 14 victims of a coal mine gas explosion with PTSD and 23 matched coal miners without experiencing the coal mine explosion were enrolled. The differences in fractional anisotropy (FA) within 7 sub-regions of the CC were compared between the two groups. Compared to the controls, PTSD coal miners exhibited significantly reduced FA values in the anterior sub-regions of the CC (P < 0.05, Bonferroni-corrected), which mainly interconnect the bilateral frontal cortices. Our findings indicated that the anterior part of the CC was more severely impaired than the posterior part in young adult-onset PTSD, which suggested the patterns of CC impairment may depend on the developmental stage of the structure when the PTSD occurs.

Corpus callosum in cognitive and sensory processing: insights into autism

ABSTRACT Atypical corpus callosum size and functional connectivity have been repeatedly implicated in autism spectrum disorders (ASDs). Conversely, individuals with agenesis of the corpus callosum often present with diagnostic features characteristic of autism. An emerging literature has identified genetic and environmental factors which may contribute to both ASD symptomatology and the neuroanatomic finding of altered white matter in the corpus callosum. In this review, we consider what is known about the structure and function of the corpus callosum and provide an update on research identifying corpus callosum abnormalities in individuals with ASD. We also review the literature on behaviors characteristic of autism that are observed in individuals with agenesis of the corpus callosum in an effort to identify some of the neuropathology that is likely to be associated with these behaviors. Finally, we suggest a conceptual model of ‘sensory processing inefficiency’ for future research aimed at elucidating some of the phenotypic variation in individuals with social communication challenges.