Explore the vast range of titles available.

To evaluate the clinical utility of genetic testing via karyotyping, chromosomal microarray analysis (CMA), and exome sequencing in cases with corpus callosum abnormalities (CCA). Here, 65 prenatal and 12 postnatal cases diagnosed with CCA via ultrasound and magnetic resonance imaging examination were enrolled. All cases were divided into two groups: 21 (27.3%) isolated and 56 (72.7%) non-isolated CCA groups. Karyotyping and CMA were first performed in parallel, then followed by whole exome sequencing (WES) after negative karyotype and CMA results. Clinical outcomes were also followed up. Karyotype abnormalities were identified in 7 cases (9.1%, 7/77). Karyotype abnormality rates in the isolated and non-isolated CCA groups were 8.0% and 9.6%, respectively ( p >  0.05). Pathogenic/likely pathogenic (P/LP) CNVs were identified in 11 cases (14.3%, 11/77), including 2(9.5%, 2/21) and 9(16.1%, 9/56) cases in the isolated and non-isolated CCA groups, respectively ( p  > 0.05). WES identified P/LP diagnostic genetic variants in 8 (47.1%, 8/17) cases, including 2 and 6 cases in the isolated and non-isolated CCA groups, respectively. Additionally, 3 cases with variants of unknown significance were identified. Of the 65 prenatal cases with CCA, 31 (47.7%) were terminated, 1 (1.5%) was a miscarriage, 33 (50.8%) yielded live born babies; of these, 4(12.1%, 4/33) yielded babies with neurodevelopment disorders (NDDs). Of the 12 postnatal cases with CCA, all presented NDDs. Genetic causes of CCA are highly variable. Prenatal brain magnetic resonance imaging and systemic ultrasound examination should be performed to examine other anomalies when CCAs are detected via ultrasound. WES is also recommended following negative karyotype and CMA results.

Objectives: Agenesis of the corpus callosum (AgCC), characterized by developmental absence of the corpus callosum, is one of the most common congenital brain malformations. To date, there are limited data on the neuropsychological consequences of AgCC and factors that modulate different outcomes, especially in children. This study aimed to describe general intellectual, academic, executive, social and behavioral functioning in a cohort of school-aged children presenting for clinical services to a hospital and diagnosed with AgCC. The influences of age, social risk and neurological factors were examined. Methods: Twenty-eight school-aged children (8 to 17 years) diagnosed with AgCC completed tests of general intelligence (IQ) and academic functioning. Executive, social and behavioral functioning in daily life, and social risk, were estimated from parent and teacher rated questionnaires. MRI findings reviewed by a pediatric neurologist confirmed diagnosis and identified brain characteristics. Clinical details including the presence of epilepsy and diagnosed genetic condition were obtained from medical records. Results: In our cohort, ~50% of children experienced general intellectual, academic, executive, social and/or behavioral difficulties and ~20% were functioning at a level comparable to typically developing children. Social risk was important for understanding variability in neuropsychological outcomes. Brain anomalies and complete AgCC were associated with lower mathematics performance and poorer executive functioning. Conclusions: This is the first comprehensive report of general intellectual, academic, executive social and behavioral consequences of AgCC in school-aged children. The findings have important clinical implications, suggesting that support to families and targeted intervention could promote positive neuropsychological functioning in children with AgCC who come to clinical attention. (JINS, 2018, 24, 445–455)

Background: Agenesis of the corpus callosum (AgCC) involves congenital absence of all or part of the corpus callosum. Because the disorder can only be firmly diagnosed via neuroradiology, it has a short research history, and only recently has the cognitive syndrome become clear. Purpose: Our purpose is to review the primary deficits in AgCC that constitute the core syndrome. Conclusions: The cores syndrome includes: (1) reduced interhemispheric transfer of sensory-motor information; (2) reduced cognitive processing speed; and (3) deficits in complex reasoning and novel problem-solving. These domains do not appear to reflect different neuroanatomical abnormalities, but rather different domains of expression of reduced interhemispheric communication from callosal absence. Implications: These core deficits are expressed across various domains of cognitive, behavioral, and social functioning. The impact of these deficits varies across development and may be moderated by individual factors such as co-occurrence of other neurodevelopmental conditions, general intellectual capacity, and environmental support. (JINS, 2019, 25, 324–330)

BackgroundAgenesis of the corpus callosum (ACC) is the most frequent commissural malformation of the brain. It continues to be an important cause of the pregnancy termination associated with the central nervous system (CNS).ObjectiveThe aim of the study is to provide a comprehensive assessment of fetuses with diagnosis of complete ACC, as well as postnatal neurodevelopmental outcomes.MethodsThe data of 75,843 fetuses were screened for evaluation of complete ACC between 2003 and 2017, and a total of 109 cases with complete ACC were included in the study. ACC was considered isolated when no additional anomalies were detected, and ACC was considered complex when additional anomalies were present.ResultsThe prevalence of complete ACC was 9.4 per 10,000 live births, and the incidence was ranged from 1.8 to 16.6 per 10,000 person-years. Patients with isolated ACC had a significantly higher survival when compared with patients with complex ACC (97.4%, n = 38/39 vs. 68.8%, n = 22/32, P = 0.001).The most important cause of death were congenital heart disease and/or respiratory failure during neonatal period. Developmental and intellectual disabilities were significantly higher in the complex ACC cases (P < 0.001). Postnatal neurodevelopmental outcomes were completely normal in 79.4% of cases with isolated ACC.ConclusionsIsolated complete ACC is usually associated with a favorable outcome. The most important prognostic factors are the presence or absence of associated congenital anomalies.

Purpose The identification and prognosis of the agenesis of the corpus callosum (ACC) for prenatal consultation are complex and currently unclear. This study aims to explore the correlated genetic mutations of prenatal ACC. Methods We retrospectively analyzed 114 prenatal cases of ACC. All cases ( n  = 114) were subjected to chromosomal microarray analysis (CMA), and 66 CMA-negative cases underwent prenatal exome sequencing (pES) for further analysis. Results CMA was diagnosed positively in 15/114 (13.2%) cases and pES was diagnosed positively in 24/66 (36.4%) CMA-negative cases. The detection rate of genetic causes between complete and partial ACCs was not significantly different ( P  > 0.05). Between isolated and non-isolated (other anomalies present) ACCs, the diagnostic rate of pES in non-isolated cases was significantly higher ( P  < 0.001), while CMA results did not differ ( P  > 0.05). The diagnostic rate of CMA was significantly increased in cases combined with intracranial and extracranial malformations ( P  = 0.014), while no CMA positivity was detected in cases combined with only intracranial malformations. Conclusion For fetuses with prenatal ACC, further pES analysis should be recommended after negative CMA results. Chromosome abnormalities are less likely to occur when ACC with only intracranial malformations combined.

Study Objectives: There is limited information about sleep in agenesis of the corpus callosum (ACC). We aim to describe the sleep architecture and respiratory parameters of children with ACC. Methods: We performed a retrospective study of 20 patients with ACC who had polysomnography between 2000 and 2023. Demographic data, body mass index or weight for length, associated conditions, and polysomnography findings were collected. National Sleep Foundation sleep quality indicators as well as increased polysomnography arousal index ≥ 10 events/h were used in the analysis. Fisher’s exact test or unpaired t test was used to compare groups. Results: Average age was 5.9 ± 5.4 years old. A total of 12/20 patients were male; 6/20 were overweight/obese; 14/20 had complete ACC, and 6/20 had partial ACC; 8/20 had seizures; 15/20 had ≥ 1 National Sleep Foundation poor sleep quality indicator (decreased sleep efficiency [45%], decreased rapid eye movement sleep [53%]); and 9/20 had increased arousals. Between complete and partial ACC, there was no difference in presence of ≥ 1 poor sleep quality indicator ( P = .61), sleep efficiency ( P = .34), rapid eye movement sleep ( P = .28), and arousals ( P = 1.0). 11/18 had obstructive sleep apnea (OSA); 5/11 had associated central sleep apnea. There was no difference in OSA between those with complete and partial ACC ( P = 1.0). OSA was associated with children < 3 years old ( P = .01). Conclusions: Children with ACC have poor sleep quality, and many have OSA. There was no difference in sleep quality or presence of OSA between those with complete and partial ACC. OSA was seen more in younger children. Our study supports the need for screening of sleep-related disorders in patients with ACC. Citation: Kwon A, Gu PK, Zhang C, Davidson Ward SL, Perez IA. Sleep disorders in pediatric patients with agenesis of the corpus callosum. J Clin Sleep Med . 2024;20(10):1663–1667.

Autism spectrum disorders (ASD) have numerous etiologies, including structural brain malformations such as agenesis of the corpus callosum (AgCC). We sought to directly measure the occurrence of autism traits in a cohort of individuals with AgCC and to investigate the neural underpinnings of this association. We screened a large AgCC cohort (n = 106) with the Autism Spectrum Quotient (AQ) and found that 45 % of children, 35 % of adolescents, and 18 % of adults exceeded the predetermined autism-screening cut-off. Interestingly, performance on the AQ’s imagination domain was inversely correlated with magnetoencephalography measures of resting-state functional connectivity in the right superior temporal gyrus. Individuals with AgCC should be screened for ASD and disorders of the corpus callosum should be considered in autism diagnostic evaluations as well.

ObjectivesTo describe the neurological phenotype of children with prenatal diagnosis of agenesis of corpus callosum (ACC) and interhemispheric cysts associated with malformations of cortical development (MCD).MethodsWe reviewed the neuroimaging, neurologic, EEG, and genetic data of 36 patients (21 males, mean age 7 years) with ACC and interhemispheric cysts. Associations were tested with Chi-squared and Fisher exact tests.ResultsAccording to the 2001 Barkovich classification, we found 4 type 1c (11.1%), 6 type 2a (16.6%), 18 type 2b (50%, 6/18 girls with Aicardi syndrome), and 9 type 2c cysts (22.2%). EEG showed specific epileptic activity in 27/36 patients (75%). Epilepsy was diagnosed in 16 subjects (16/36, 44.4%), including all Aicardi patients, and was associated with cognitive impairment (p = 0.032). Severe intellectual disability and epilepsy were associated with type 2b cysts, always due to Aicardi patients (p < 0.05). After excluding Aicardi patients, all subjects with type 2b cysts had mild neurological phenotype. Patients with 2a and 2c cysts more frequently had normal cognition (83.3% and 62.5% of cases, respectively). Patients with type 1c cyst mostly had mild/moderate cognitive impairment. Severe neurologic deficits were associated with 1c cysts and 2b cysts with Aicardi syndrome (p < 0.05). Multilobar and/or bilateral MCD were associated with severe neurological and epileptic phenotypes (p < 0.05).ConclusionOnce excluded Aicardi syndrome, most patients with ACC and interhemispheric cysts have a mild clinical phenotype characterized by borderline/normal cognition and minor neurological signs. Despite the high prevalence of EEG epileptic abnormalities, epilepsy in these cases is infrequent and usually responsive to antiepileptic drugs.

Impoverished capacity for social inference is one of several symptoms that are common to both agenesis of the corpus callosum (AgCC) and Autism Spectrum Disorder (ASD). This research compared the ability of 14 adults with AgCC, 13 high-functioning adults with ASD and 14 neurotypical controls to accurately attribute social meaning to the interactions of animated triangles. Descriptions of the animations were analyzed in three ways: subjective ratings, Linguistic Inquiry and Word Count, and topic modeling (Latent Dirichlet Allocation). Although subjective ratings indicated that all groups made similar inferences from the animations, the index of perplexity (atypicality of topic) generated from topic modeling revealed that inferences from individuals with AgCC or ASD displayed significantly less social imagination than those of controls.

BackgroundAutism spectrum disorders (ASD) are a group of poorly understood behavioural disorders, which have increased in prevalence in the past two decades. Animal models offer the opportunity to understand the biological basis of these disorders. Studies comparing different mouse strains have identified the inbred BTBR T + tf/J (BTBR) strain as a mouse model of ASD based on its anti-social and repetitive behaviours. Adult BTBR mice have complete agenesis of the corpus callosum, reduced cortical thickness and changes in early neurogenesis. However, little is known about the development or ultimate organisation of cortical areas devoted to specific sensory and motor functions in these mice that may also contribute to their behavioural phenotype.ResultsIn this study, we performed diffusion tensor imaging and tractography, together with histological analyses to investigate the emergence of functional areas in the cerebral cortex and their connections in BTBR mice and age-matched C57Bl/6 control mice. We found evidence that neither the anterior commissure nor the hippocampal commissure compensate for the loss of callosal connections, indicating that no interhemispheric neocortical connectivity is present in BTBR mice. We also found that both the primary visual and somatosensory cortical areas are shifted medially in BTBR mice compared to controls and that cortical thickness is differentially altered in BTBR mice between cortical areas and throughout development.ConclusionsWe demonstrate that interhemispheric connectivity and cortical area formation are altered in an age- and region-specific manner in BTBR mice, which may contribute to the behavioural deficits previously observed in this strain. Some of these developmental patterns of change are also present in human ASD patients, and elucidating the aetiology driving cortical changes in BTBR mice may therefore help to increase our understanding of this disorder.