Complete Agenesis Of The Corpus Callosum Research Articles

Genotype-phenotype correlation in CLCN4-related developmental and epileptic encephalopathy.

CLCN4-related disorder is a rare X-linked neurodevelopmental condition with a pathogenic mechanism yet to be elucidated. CLCN4 encodes the vesicular 2Cl-/H+ exchanger ClC-4, and CLCN4 pathogenic variants frequently result in altered ClC-4 transport activity. The precise cellular and molecular function of ClC-4 remains unknown; however, together with ClC-3, ClC-4 is thought to have a role in the ion homeostasis of endosomes and intracellular trafficking. We reviewed our research database for patients with CLCN4 variants and epilepsy, and performed thorough phenotyping. We examined the functional properties of the variants in mammalian cells using patch-clamp electrophysiology, protein biochemistry, and confocal fluorescence microscopy. Three male patients with developmental and epileptic encephalopathy were identified, with differing phenotypes. Patients #1 and #2 had normal growth parameters and normal-appearing brains on MRI, while patient #3 had microcephaly, microsomia, complete agenesis of the corpus callosum and cerebellar and brainstem hypoplasia. The p.(Gly342Arg) variant of patient #1 significantly impaired ClC-4's heterodimerization capability with ClC-3 and suppressed anion currents. The p.(Ile549Leu) variant of patient #2 and p.(Asp89Asn) variant of patient #3 both shift the voltage dependency of transport activation by 20 mV to more hyperpolarizing potentials, relative to the wild-type, with p.(Asp89Asn) favouring higher transport activity. We concluded that p.(Gly342Arg) carried by patient #1 and the p.(Ile549Leu) expressed by patient #2 impair ClC-4 transport function, while the p.(Asp89Asn) variant results in a gain-of-transport function; all three variants result in epilepsy and global developmental impairment, but with differences in epilepsy presentation, growth parameters, and presence or absence of brain malformations.

Diagnostic yield of exome sequencing in prenatal agenesis of corpus callosum: systematic review and meta-analysis.

To determine the incremental diagnostic yield of exome sequencing (ES) after negative chromosomal microarray analysis (CMA) in cases of prenatally diagnosed agenesis of the corpus callosum (ACC) and to identify the associated genes and variants. A systematic search was performed to identify relevant studies published up until June 2022 using four databases: PubMed, SCOPUS, Web of Science and The Cochrane Library. Studies in English reporting on the diagnostic yield of ES following negative CMA in prenatally diagnosed partial or complete ACC were included. Authors of cohort studies were contacted for individual participant data and extended cohorts were provided for two of them. The increase in diagnostic yield with ES for pathogenic/likely pathogenic (P/LP) variants was assessed in all cases of ACC, isolated ACC, ACC with other cranial anomalies and ACC with extracranial anomalies. To identify all reported genetic variants, the systematic review included all ACC cases; however, for the meta-analysis, only studies with ≥ three ACC cases were included. Meta-analysis of proportions was employed using a random-effects model. Quality assessment of the included studies was performed using modified Standards for Reporting of Diagnostic Accuracy criteria. A total of 28 studies, encompassing 288 prenatally diagnosed ACC cases that underwent ES following negative CMA, met the inclusion criteria of the systematic review. We classified 116 genetic variants in 83 genes associated with prenatal ACC with a full phenotypic description. There were 15 studies, encompassing 268 cases, that reported on ≥ three ACC cases and were included in the meta-analysis. Of all the included cases, 43% had a P/LP variant on ES. The highest yield was for ACC with extracranial anomalies (55% (95% CI, 35-73%)), followed by ACC with other cranial anomalies (43% (95% CI, 30-57%)) and isolated ACC (32% (95% CI, 18-51%)). ES demonstrated an incremental diagnostic yield in cases of prenatally diagnosed ACC following negative CMA. While the greatest diagnostic yield was observed in ACC with extracranial anomalies and ACC with other central nervous system anomalies, ES should also be considered in cases of isolated ACC. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Tela-choroidea-to-anterior-cerebral-artery distance (TACAD): novel marker on color Doppler to identify fetuses with complete or partial agenesis of corpus callosum.

To assess objectively the course of the anterior cerebral artery (ACA) by measuring its distance to the tela choroidea in the midsagittal view, and to compare this distance in normal fetuses with that in those with agenesis of the corpus callosum (ACC), a condition known to be associated with an abnormal course of the ACA. The tela-choroidea-to-anterior-cerebral-artery distance (TACAD) was measured in the midsagittal view of the brain on color Doppler, between the anterior border of the tela choroidea and the ACA at the level of the callosal genu. Reference ranges in relation to gestational age were established in a prospective, cross-sectional study of 253 normal healthy fetuses between 19 and 36 weeks of gestation. The study group included fetuses with complete ACC (n = 28) or partial ACC (n = 18). TACAD of normal fetuses showed an increase during the second half of pregnancy, with a mean value of 10.1 mm and 14.2 mm at 22 and 30 weeks of gestation, respectively. All (28/28) fetuses with complete ACC and 83% (15/18) of those with partial ACC had significantly shorter TACAD, with mean values of 3.9 mm and 6.6 mm, respectively. TACAD is a measurement that is simple to obtain during fetal color Doppler neurosonography, which enables quantification of the course of the ACA and pericallosal artery. TACAD is shorter in fetuses with complete or partial ACC than in normal fetuses and provides an objective, quantifiable value, rather than merely descriptive information. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

3 Emotional Expression in Infants with Agenesis of the Corpus Callosum: The Role of Callosal Connectivity in Early Temperament

Objective:Accumulating evidence suggests that corpus callosum development is critically involved in the emergence of behavioral and cognitive skills during the first two years of life and that structural abnormalities of the corpus callosum are associated with a variety of neurodevelopmental disorders. Indeed by adulthood ∼30% of individuals with agenesis of the corpus callosum (ACC), a congenital condition resulting in a partial or fully absent corpus callosum, exhibit phenotypic features consistent with autism spectrum disorder (ASD). However, very little is known about developmental similarities and/or differences among infants with ACC and infants who develop ASD. This study describes temperament in infants with ACC during the first year of life in comparison with a neurotypical control group. Additionally, it examines the potential contribution of disrupted callosal connectivity to early expression of temperament in ASD through comparison to children with high familial likelihood of ASD.Participants and Methods:Longitudinal ratings of positive and negative emotionality were acquired at 6 and 12 months on the Infant Behavior Questionnaire-Revised across four groups of infants: isolated complete and partial ACC (n=104), high familial likelihood of ASD who do and do not have a confirmed ASD diagnosis (HL+ n=81, HL- n=282), and low-likelihood controls (LL- n=152).Results:Overall, the ACC group demonstrated blunted affect, with significantly lower positive and negative emotionality than LL controls at both timepoints. Specifically, the ACC group exhibited lower activity and approach dimensions of positive emotionality at both timepoints, with lower high-intensity pleasure at 6 months and lower vocal reactivity at 12 months. On negative emotionality subscales, the ACC group exhibited lower distress to limitations and sadness at both timepoints, as well as lower falling reactivity at 6 months. The ACC and HL groups did not differ significantly on positive emotionality at either timepoint. However, negative emotionality was lower in the ACC group than the HL- group at both timepoints and lower than the HL+ group at 12 months, with lower distress to limitations and sadness ratings than both HL groups at both timepoints.Conclusions:These findings highlight the importance of interhemispheric connections in facilitating active engagement and pursuit of pleasurable activities during the first year of life, as well as expression of sadness and distress to limitations. Notably, similarities between infants with ACC and infants at elevated familial risk of ASD suggest that disrupted callosal connectivity may specifically contribute to reductions in positive emotionality.

The “cortical invagination sign”: a midtrimester sonographic marker of unilateral cortical focal dysgyria in fetuses with complete agenesis of the corpus callosum

Agenesis of the corpus callosum is associated with several malformations of cortical development. Recently, features of focal cortical dysgyria have been described in fetuses with agenesis of the corpus callosum. This study aimed to describe the "cortical invagination sign," a specific sonographic feature of focal cortical dysgyria, which is consistently seen at midtrimester axial brain ultrasound in fetuses with complete agenesis of the corpus callosum. This was a retrospective analysis of prospectively collected data from 2018 to 2021, including patients referred to 5 fetal medicine centers in the second trimester of pregnancy (19 0/7 to 22 0/7 weeks of gestation) with suspected complete agenesis of the corpus callosum. All cases with the diagnosis of complete agenesis of the corpus callosum were submitted to an axial sonographic assessment of the fetal brain on the transventricular plane. In this scanning section, the mesial profile of both cerebral hemispheres at the level of the frontal-parietal cortex was investigated. In this area, the operator looked for an abnormal invagination of the cortical surface along the widened interhemispheric fissure, which was referred to as the "cortical invagination sign." All fetuses were submitted to dedicated antenatal magnetic resonance imaging to reassess the ultrasound findings. Cases with additional brain anomalies, which did not involve the cortex, were excluded. The final diagnosis was confirmed at postnatal brain magnetic resonance imaging or postmortem examination, for cases undergoing termination of pregnancy. The primary outcome of this study was to evaluate the presence and laterality of the "cortical invagination sign" in fetuses with complete agenesis of the corpus callosum at antenatal ultrasound and magnetic resonance imaging. During the study period, 64 cases of complete agenesis of the corpus callosum were included; of those cases, 50 (78.1%) resulted in termination of pregnancy, and 14 (21.9%) resulted in a live birth. The "cortical invagination sign" was detected at ultrasound in 13 of 64 cases (20.3%) and at targeted brain magnetic resonance imaging in 2 additional cases (23.4%), all of which were electively terminated. Moreover, the "cortical invagination sign" was found to be exclusively unilateral and on the left cerebral hemisphere in all the cases. There was a predominant number, although nonsignificant, of male fetuses (80.0% of cases; P=.06) in the group of complete agenesis of the corpus callosum with the "cortical invagination sign." The "cortical invagination sign" is a specific marker of focal cortical dysgyria, which seems to characterize at midtrimester of pregnancy in a large group of fetuses with complete agenesis of the corpus callosum. The etiology, pathophysiology, and prognostic significance of this finding remain to be elucidated.

GR.1 Different functional consequences result in different phenotypes in CLCN4-related developmental and epileptic encephalopathy

Background: Variants in CLCN4 are implicated in neurodevelopmental disorder, X-linked intellectual disability, and epileptic encephalopathy. CLCN4 encodes ClC-4, which is hypothesized to play a role in ion homeostasis and intracellular trafficking. ClC-4 relies on its formation of heterodimers with ClC-3, which possesses signals for target organelles. Methods: Case-Series. Then, we performed heterologous expression, patch-clamp electrophysiology, confocal microscopy, and protein biochemistry experiments to characterize our patients’ ClC-4 variants. Results: All three male patients had developmental and epileptic encephalopathy. Patients #1 and #2 had normal-appearing brains on MRI and no dysmorphic features. Patient #3 had: microcephaly, microsomia, complete agenesis of the corpus-callosum; and, cerebellar and brainstem hypoplasia. Patient #1 had recurrent status epilepticus separated by months of seizure freedom, while Patient #2 and #3 had brief, daily seizures. The p.Gly342Arg variant impaired the heterodimerization capability of ClC-4. The p.Ile549Leu and p.Asp89Asn variants exhibited early transport-activation, with p.Asp89Asn favouring higher transport-activity of ClC-4. Conclusions: We extend the phenotypic spectrum of CLCN4 variants and demonstrate the pathological functional-consequences of three previously unclassified variants. The p.Gly342Arg variant lead to a loss-of-function phenotype; however, the p.Ile549Leu and p.Asp89Asn variants likely caused gain-of-function phenotypes. Targeted animal or induced pluripotent stem-cell models are needed to further understand epileptogenic mechanisms of CLCN4 variants.

Unravelling the Clinical Co-Morbidity and Risk Factors Associated with Agenesis of the Corpus Callosum.

Agenesis of the Corpus Callosum (ACC) can result in multiple neurological deficits including social and behavioural issues. However, the underlying aetiology, clinical co-morbidity and the contributing risk factors remain elusive, resulting in inaccurate prognosis and delayed therapy. The main objective of this study was to comprehensively describe the epidemiology and clinical co-morbidity associated with patients diagnosed with ACC. The secondary objective was to identify the factors that contribute towards increased risk for ACC. For this, we analysed 22 years (1998-2020) of clinical data across the whole of Wales, UK collected through the Congenital Anomaly Register & Information Service (CARIS) and Public Health Wales (PHW). Our results demonstrate that complete ACC (84.1%) was the prevalent subtype, in comparison to partial ACC. Further, ventriculomegaly/hydrocephalus (26.37%) and ventricular septal defect (21.92%) were identified to be the most prevalent neural malformation (NM) and congenital heart disorder (CHD) in our cohort. Although 12.7% of subjects with ACC had both an NM and CHD, we found no significant association between them (χ2 (1, n = 220) = 3.84, p = 0.33). We found socioeconomic deprivation and increased maternal age contributed towards an increased risk for ACC. To the best of our knowledge, this study for the first time defines the clinical phenotypes and the factors that contribute to ACC within the Welsh population. These findings will be of value to both patients and healthcare professionals, who may take preventative or remedial measures.

First‐trimester ventriculomegaly in fetuses with callosal agenesis: Cause or association?

The sonographic findings in four fetuses presenting with ventriculomegaly at first-trimester ultrasound that were subsequently diagnosed as having agenesis of the corpus callosum (ACC) are described. The diagnosis of early ventriculomegaly was suspected subjectively by identification of increased cerebrospinal fluid within the lateral ventricles and confirmed by measuring choroid plexus-to-lateral ventricle length and area ratios. Subsequent scans revealed complete ACC in two cases and partial ACC in the other two. This report adds to the increasing evidence suggesting that first-trimester ventriculomegaly is a strong sonographic marker of underlying brain anomalies, including less evident malformations such as ACC. Detailed second-trimester fetal neurosonography in those women continuing their pregnancies should be performed.

Early Fetal Corpus Callosum: Demonstrating Normal Growth and Detecting Pathologies in Early Pregnancy.

A malformed corpus callosum carries a risk for abnormal neurodevelopment. The advent of high-frequency transducers offers the opportunity to assess corpus callosum development in early pregnancy. The aim of the study was to construct a reference chart of the fetal corpus callosum length on ultrasound between 13 and 19 weeks of gestation and to prospectively examine growth patterns in pathologic cases. We performed a prospective cross-sectional study between 2020 and 2022 in well-dated, low-risk, singleton pregnancies between 13 and 19 weeks of gestation. A standardized image was obtained in the midsagittal plane. Imaging criteria were used as a confirmation of the early corpus callosum. Measurements were taken by 4 trained sonographers. Intra- and interobserver variability was assessed. Corpus callosum length in centiles were calculated for each gestational week. One hundred eighty-seven fetuses were included in the study. All cases met inclusion criteria. At 13 weeks of gestation, the margins of the early corpus callosum were sufficiently clear to be measured in 80% (20/25) of fetuses. A cubic polynomial regression model best described the correlation between corpus length and gestational age. The correlation coefficient (r 2) was 0.929 (P < .001). Intra- and interobserver variability had high interclass correlation coefficients (>0.99). Presented is the earliest published case of agenesis of corpus callosum and a case of dysgenetic corpus callosum in Rubinstein-Taybi syndrome. Provided is a nomogram of the early fetal corpus callosum. Applying imaging criteria helped to identify a case of complete agenesis of the corpus callosum as early as 14 weeks.

Agenesis of the Corpus Callosum, Cardiac, Ocular, and Genital Syndrome with Interhemispheric Cyst in an Infant: A Case Report

In rural India, it is fairly common for infants to be brought in with symptoms such as failure to gain weight and a history of recurrent respiratory tract infections. Congenital Heart Disease (CHD) is often associated with various syndromes, including Down syndrome, Turner syndrome, Holt-oram, and others. It is widely understood and practiced to investigate for other systemic and congenital anomalies when a child is suspected or diagnosed with CHD or any other congenital condition. On the other hand, one of the most prevalent malformations of the cerebral cortex involves the corpus callosum. The corpus callosum consists of white matter tracts that connect the left and right cerebral hemispheres. Agenesis of the Corpus Callosum (ACC), which can be partial or complete, may occur alone or in combination with other cerebral abnormalities. It can manifest as hypoplasia or complete absence of the corpus callosum. In the present case report, the authors present a three-month-old infant who presented with complaints of failure to gain weight and a history of convulsions despite being on anticonvulsant medication. Further evaluation revealed complete agenesis of the corpus callosum on Magnetic Resonance Imaging (MRI). Additional examination findings included microcephaly, left-sided microphthalmia, low-set ears, retrognathia, suggesting a dysmorphic facies, and a left-sided inguinal hernia. The patient was also diagnosed with Patent Ductus Arteriosus (PDA) based on a 2D echo. The presence of multiple systemic anomalies in the present case makes it a rare occurrence, with only a few similar cases reported.

Apert Syndrome with Agenesis of the Corpus Collosum - Case Report

Abstract Apert syndrome (Acrocephalosyndactylia type 1) belongs to the group of extremely rare congenital dysmorphic syndromes. It is characterized by craniostenosis with very early fusion of the skull and / or cranial base sutures, facial hypoplasia, symmetrical syndactyly of the fingers and toes and other systemic malformations. Multiple CNS abnormalities are common, but simultaneous occurrence of Apert syndrome and agenesis of corpus callosum is estimated about 10%. We present a male patient born after first, normal and controlled pregnancy and term, naturally birth, in which the Apert syndrome was diagnosed, based on the clinical presentation of the skull and face and syndactyly of fingers and toes. Neurological examination established generalized hypotonia and aggravated provocation of the primitive reflexes. Neurosonography showed complete agenesis of the corpus callosum, which makes this case a rare form of this syndrome. The head X-rays showed turricephalic skull shape and suture’s synostoses, which is demonstrated in more detail at computed tomography finding. The hands and feet X-rays showed bone synostosis of fingers and toes. The video-electroencephalogram recorded intermittent depression of electrocortical activity. There was conducted the multidisciplinary examination in order to examine the possibility of reconstructive and plastic surgical correction of the anomalies. The neurodevelopmental disorders in patients with Apert syndrome can be manifested by a variety of congenital malformations, but considering its rare occurrence, the significance of these abnormalities remains unknown.

Complete agenesis of corpus callosum and unilateral cortical formation anomalies detected on fetal MR imaging: a phenotype strongly associated with the male fetuses.

In a previous study of classifying fetuses with cortical formation abnormalities (CFA) with fetal MR, we noticed a cluster of cases with unilateral CFA and complete agenesis of the corpus callosum (ACC). In this study, we provide a detailed morphological analysis of such fetuses using fetal MR to determine if there are indicators (such as the gender of the fetus) that could be used to delineate a genetic substrate of the phenotype in order to inform future studies. We have studied 45 fetuses with the unilateral CFA/ACC phenotype and analysed through an expert consensus panel the location and fine detail of the CFA and the associated findings such as associated anomalies, head size, and sex of the fetus. The frontal lobe was significantly more frequently involved by CFA when compared with other lobes (p < 0.001) but no preference for the left or right hemisphere. CFA most often consisted of excessive/dysmorphic sulcation. The CFA/ACC phenotype was overwhelmingly more frequent in male fetuses (M:F 4.5:1-p < 0.0001). The most frequent associated findings were: ventriculomegaly (16/45 fetuses) and interhemispheric cysts (12/45 cases). This report highlights the specific phenotype of unilateral CFA/ACC that is much more common in male fetuses. This finding provides a starting point to study possible sex-linked genetic abnormalities that underpin the unilateral CFA/ACC phenotype. • We collected fetuses with unilateral cortical formation abnormality and callosal agenesis. • That distinctive neuroimaging phenotype has a strong male gender prevalence (over 80%). • This observation forms the basis of studies about outcomes and genetic substrates.

Long-term outcome of consecutive case series of congenital isolated agenesis of corpus callosum.

To describe the long-term outcome of children with prenatally diagnosed isolated complete agenesis of the corpus callosum (cACC). In this single-center case series, we reviewed retrospectively the charts of fetuses referred to our fetal therapy unit from January 2004 to July 2020 for a suspected anomaly of the corpus callosum (CC). Cases with prenatally diagnosed isolated cACC were included. Fetal karyotype and comparative genomic hybridization microarray of amniotic fluid, in addition to fetal magnetic resonance imaging, were offered to all pregnant women with a diagnosis of fetal CC malformation. The surviving children were enrolled in the neurodevelopmental follow-up program at our institution, which included postnatal magnetic resonance imaging, serial neurological examinations and neurodevelopmental evaluations with standardized tests according to age. Families living in remote areas or far from our institution were offered a structured ad-hoc phone interview. A total of 128 pregnancies with fetal CC malformation were identified (mean gestational age at diagnosis, 24.5 (range, 21-34) weeks), of which 53 cases were diagnosed prenatally with apparently isolated cACC. Of these, 12 cases underwent termination of pregnancy, one resulted in intrauterine demise at 24 weeks of gestation and 13 cases were lost to follow-up. Of the remaining 27 children, one was excluded due to an associated chromosomal anomaly (8p21.3q11.21 mosaic duplication) diagnosed after birth, which could have been detected prenatally if the parents had consented to amniocentesis. In the 26 children included in the analysis, neurodevelopmental follow-up was available for a median of 3 (range, 1-16) years. Three (11.5%) infants had severe neurodevelopmental impairment, two of which were diagnosed postnatally with a genetic syndrome (Mowat-Wilson syndrome and Vici syndrome) that would not have been diagnosed prenatally. Seven (26.9%) children had mild neurodevelopmental impairment and 16 (61.5%) had normal neurodevelopmental outcome. The Full-Scale Intelligence Quotients of the three children with severe neurodevelopmental impairment were 50, 64 and 63, respectively, while that of the remaining children was in the normal range (median, 101; range, 89-119). In 88% of the children with cACC included in this study, neurodevelopment was not severely impaired. However, long-term follow-up is recommended in all cases of congenital isolated cACC to recognize subtle neurodevelopmental disorders as early as possible. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Outcome of Agenesis of the Corpus Callosum Diagnosed by Fetal MRI

BackgroundFetal magnetic resonance imaging (MRI) is increasingly utilized for prenatal diagnosis of agenesis of the corpus callosum (ACC). This study aimed to (1) describe cases of ACC diagnosed by fetal MRI, (2) determine the frequency of postnatal confirmation by MRI, and (3) understand postnatal outcomes of infants with ACC. MethodsMaternal records from Children's National Hospital between January 2012 and June 2019 with a prenatal neurological consultation, fetal MRI, and ACC on imaging were included. Maternal, prenatal, and postnatal infant data were collected. Each case was categorized as complete or partial ACC and isolated or complex ACC by fetal MRI and group comparisons of outcomes were analyzed. ResultsA total of 127 maternal-fetal dyads with ACC were categorized into 45 isolated-complete, 17 isolated-partial, 46 complex-complete, and 19 complex-partial ACC. Of 75 live births, 72 had postnatal evaluations. In 43 of 59 (73%) cases with postnatal neuroimaging, prenatal ACC subcategory was confirmed. Children with isolated or complex and with partial or complete ACC had similar rates of developmental delays and epilepsy. Complex ACC cases had worse outcomes than isolated ACC, with complex ACC having more postnatal dysmorphisms and abnormal feeding and vision compared with isolated ACC. Similar neurodevelopmental outcomes were seen for partial and complete ACC. ConclusionsChildren with isolated or complex ACC and with partial or complete ACC have a range of neurodevelopmental outcomes. Fetal and postnatal brain MRI is a valuable tool to understand differences of the corpus callosum that can guide genetic testing, prenatal counseling, and postnatal care.

Assessment of pericallosal artery at 11-14 weeks of gestation: Cohort study and meta-analysis.

To report the rate of visualization of the pericallosal artery (PCA) in the first trimester of pregnancy (11-14 weeks). Prospective observational study of consecutive fetuses undergoing first trimester risk assessment for chromosomal anomalies. The presence of PCA was assessed in a midsagittal view of fetal brain using high-definition power Color Doppler. A normal course of the PCA was defined as the visualization of an artery emerging from the anterior cerebral artery running parallel the corpus callosum (CC). The reference standard was the visualization of CC and PCA between the 20 and 22 weeks of gestation. We also performed a systematic review and meta-analysis of the published literature. Multivariate logistic regression and random-effect meta-analyses of proportion were used to analyze the data. Cohort study: Five-hundred women were included. PCA was identified trans-abdominally or transvaginally at 11-14 weeks of gestation in 98.8% (95% CI 97.4-99.6: 494/500); of the four cases of PCA not identified one had a diagnosis of complete agenesis of the corpus callosum during the anomaly scan which was confirmed at birth. Systematic review of the published literature: Six studies (1093 fetuses, including the present series) were included. The PCA was detected at the 11-14 weeks scan and confirmed to co-exist with a normal CC at time of the anomaly scan in 96.9% (95% CI 93.8-99.0); 20.6% (95% CI 5.7-41.7) of fetuses with no clear identification of the PCA at the 11-14 weeks scan had a normal appearance of the CC at the time of anomaly scan. Prenatal ultrasonography has a high diagnostic accuracy in detecting PCA in the first trimester. Visualization of the PCA at the time of 11-14 scan is highly specific for the presence of a normal CC later in pregnancy.

Clinical Pattern and Associated Comorbidities of Corpus Callosum Agenesis- A Tertiary Hospital Study

Background: The corpus callosum is the main commissural bundle of fibers interconnecting the two cerebral hemispheres. Defective embryogenesis during 8 and 20 weeks of gestation can lead to partial or complete agenesis of the corpus callosum.&#x0D; Objective: To see the patient’s clinical, neurophysiological profile, and comorbidities with corpus callosum agenesis presented in tertiary care hospital.&#x0D; Materials &amp;Methods: This descriptive cross-sectional study was conducted in the department of Paediatric Neurology, BSMMU, Dhaka, from January to December 2018. Patients who were diagnosed clinically and neuro-radiologically as corpus callosum agenesis were included in this study.&#x0D; Results:Out of 20 patients, 45% were in 13-24 months and 30% were in the 0-12 months’ age group. Female patients (55%) were predominant.Forty percent of patients had microcephaly and 30% facial dysmorphism. The majority of patients presented with developmental delay (90%), followed by epilepsy, speech impairment, and mental retardation. About one-fourth (25%) of patients were diagnosed as quadriplegic cerebral palsy and one-third (30%) dyskinetic cerebral palsy. Abnormal ophthalmological findings were found in 40% of cases. EEG showed hypsarrhythmia in 30%, partial seizure with secondary generalization in 15%, and myoclonic epilepsy in 15% of patients.&#x0D; Conclusion: In this study, common clinical features of patients with corpus callosal agenesis were developmental delay, facial dysmorphism, and microcephaly. About half of the patients had epilepsy, speech impairment, and mental retardation. About two-thirds of the patients had EEG changes and the most common EEG change was hypsarrhythmia.&#x0D; BANGLADESH J CHILD HEALTH 2021; VOL 45 (1) : 10-14

A-27 A Pediatric Case Study of Neurodevelopmental Disorder Associated with Complete Agenesis of the Corpus Callosum

Abstract Objective The corpus callosum is a major white matter pathway of the brain that coordinates the transfer of information between both cerebral hemispheres. Children with complete agenesis of the corpus callosum (ACC) are at increased risk for neurodevelopmental disorders, epilepsy, and genetic abnormalities. Method This case study presents the neuropsychological profile of a 6-year-old girl in the 1st grade who was born with complete ACC and presented with a history of attention problems and behavioral-emotional difficulties. Results Neuropsychological testing revealed mild to severe deficits in attention, executive functioning, and self-regulation in the context of average intellectual functioning and broadly average to above-average academic achievement. Conclusions School recommendations included establishing a 504 plan and weekly counseling sessions with the school social worker in order to provide accommodations to support the child’s attention difficulties in the academic setting. Recommendations for genetic testing and ongoing monitoring by the patient’s neurologist were suggested given the higher rates of genetic abnormalities and seizures in children with ACC as these conditions can adversely impact neurodevelopmental outcomes. Medication management, as well as private behavior therapy with a parent-training component, were recommended for interventions to address the child’s deficits with attention and behavioral regulation. This case study demonstrates the need for prompt neuropsychological evaluation for children with ACC in order to more efficiently facilitate access to targeted assessments and treatments that can lead to improved outcomes.

Fetal MRI vs. fetal ultrasound in the diagnosis of pathologies of the central nervous system

Abstract Background Malformations of the central nervous system (CNS) constitute the 2nd most common group of fetal pathologies, which can be reflected throughout the patient's life. Fetal ultrasound (US), together with fetal magnetic resonance imaging (MRI) are extremely important techniques for the diagnosis of CNS malformations. The objective of this work was to address fetal US and fetal MRI, as well as the benefits of its use in different CNS pathologies and to ascertain which of the techniques presents better results. Methods For this systematic literature review, a search was conducted using databases such as PubMed® and ScienceDirect®, Google Scholar, b-on digital library, in a 10-year period, 2010 to 2020. 60 references were used, which met the inclusion criteria, namely compliance with the defined timeframe and the theme of the work to be addressed. Results As for the results, fetal US is the first-line technique for fetal evaluation, and its objective is to detect possible fetal malformations early, while fetal MRI complements the information collected through fetal US. When there are cases of isolated ventriculomegaly and complete agenesis of the corpus callosum, fetal US can correctly assess the pathology. When it comes to pathologies such as dysgenesis of the corpus callosum and malformations of the posterior fossa, fetal MRI evaluates more effectively in comparison to fetal US. Conclusions In conclusions, to reduce the number of false positives, the techniques should be used together, thus providing a better diagnosis.

Morphology and Morphometry of Foetal Corpus Callosum Using MRI – A Retrospective Study

Introduction: Corpus callosum (CC) is the largest commissural white fibres interconnecting cerebral hemispheres. The corpus callosum is responsible for interhemispheric transfer of information which is essential for cognitive function. The foetal corpus callosum serves as sensitive indicator for normal brain development and maturation. As the corpus callosum is a part of the highest order latest maturing mental network of the brain, its measurements are important to assess normal brain development and to locate structural changes. A comprehensive evaluation of normal human foetal corpus callosal development is essential to detect and understand the congenital anomalies of the brain. Thus, the prenatal diagnosis of partial or complete agenesis of the corpus callosum is important for predicting the normal development of the foetus. Foetal neural anomalies that are suspected on prenatal ultrasonography (USG) can be detected in early stage using foetal MRI. This imaging technique is highly useful for detailed visualization of normal neural development. Certain conditions like colpocephaly and widening of interhemispheric fissure can be clearly visualized using foetal MRI when compared to prenatal ultrasonography. Aim and objective: Was to establish the normal reference values for the measurement of foetal corpus callosum. The length and thickness of the foetal CC was measured corresponding to gestational age (GA) between 18-36weeks. Materials and methods: A retrospective MRI study was carried out in Radiology department of Sri Ramachandra Hospital. The study was conducted on 50 pregnant women with GA of 18-32 weeks and morphology of foetal corpus callosum was measured using MRI. The corpus callosum was visualized in a mid-sagittal plane as an anechoic structure, delimited by two echogenic lines superiorly by sulcus of the corpus callosum and inferiorly by the septum pellucidum. The length of corpus callosum was measured from the anterior most aspect of genu to the posterior most aspect of the splenium and the width of individual parts were measured and correlated with gestational age. The values obtained from the study were statistically calculated using regression coefficient method. Results: In the present study following parameters were observed such as length and width of diverse parts of Corpus callosum. The length of foetal CC ranged from 25.96 to 47.2 mm in 18 to 32 weeks of gestational age. The range of width of rostrum, genu, body and splenium were 1.2 to 2.2 mm, 1.2-2.8mm, 1.3-3.1mm and 1.36-3.2mm respectively. Conclusion: The periodic development of nervous system can be calculated more effectively with the morphometric measurement of foetal CC and its correlation with BPD. It is considered to be accurate than using BPD measurement of head circumference in USG. Hence, with the normative data of foetal CC measurements correlated with gestational age would give us accurate details of neuronal growth rather than measuring biparietal diameter (BPD) alone using USG. This knowledge will be highly helpful for the gynaecologists to predict the abnormal development of the foetus and it is advised to include foetal CC parameters as a one of the tools for early detection of CNS anomalies.

Heterogeneity in defining fetal corpus callosal pathology: systematic review.

Fetal anomalies of the corpus callosum (CC) have been reported in the prenatal imaging literature since 1985, and, especially when isolated, pose challenges for both the patient and fetal medicine specialist. The purpose of this study was to review systematically the literature on prenatally diagnosed abnormalities of the CC, focusing on the terminology used to describe abnormalities other than complete agenesis of the CC, and to assess the heterogeneity of the nomenclature and definitions used. This study was conducted in accordance with the PRISMA statement for reporting systematic reviews. A literature search was performed to identify prospective or retrospective case series or cohort studies, published in English, French, Italian, German or Spanish, reporting fetal imaging findings and describing anomalies of the CC. Quality and risk of bias of the studies were evaluated using the Newcastle-Ottawa scale and a modification of the scale developed by Conde-Agudelo et al. for other fetal imaging studies. The data extracted included the number of patients, the number of different anomalies identified, the descriptive names of the anomalies, and, where applicable, the definitions of the anomalies, the number of cases of each type of anomaly and the biometric charts used. Secondary tests used to confirm the diagnosis, as well as the postnatal or post-termination tests used to ascertain the diagnosis, were also recorded. The search identified 998 records, and, after review of titles and abstracts and full review of 45 papers, 27 studies were included initially in the review, of which 24 were included in the final analysis. These 24 studies had a broad range of quality and risk of bias and represented 1135 cases of CC anomalies, of which 49% were complete agenesis and the remainder were described using the term partial agenesis or nine other terms, of which five had more than one definition. In comparison to the postnatal literature, in the prenatal literature there is much greater heterogeneity in the nomenclature and definition of CC anomalies other than complete agenesis. This heterogeneity and lack of standard definitions in the prenatal literature make it difficult to develop large multicenter pooled cohorts of patients who can be followed in order to develop a better understanding of the genetic associations and neurodevelopmental and psychological outcomes of patients with CC anomalies. As this information is important to improve counseling of these patients, a good first step towards this goal would be to develop a simpler categorization of prenatal CC anomalies that matches better the postnatal literature. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.