Agenesis Of Corpus Callosum Research Articles

Acrocallosal syndrome: Classical findings in a case report with a literature review

We present a case of a 1-day-old neonate with classical findings of acrocallosal syndrome. The child presented with difficulty in feeding. Clinically, the patient had craniofacial anomalies and digital malformations. Imaging with ultrasonography and magnetic resonance imaging revealed characteristic features of corpus callosum agenesis with dandy walker malformation. A classical case of acrocallosal syndrome with sporadic occurrence is discussed with a detailed review of all such previously reported cases in the literature till date and a discussion of possible differentials.

Rare cause of dementia in childhood

AbstractBackgroundDementia is rare in paediatric age group. While inborn errors of metabolism account for majority of the causes, structural abnormalities are also responsible for cognitive decline in few patients. We present such a rare case here.MethodAn eight year old female presented to Neurology department with complaints of decline in memory, poor judgement and social disinhibition since two months with three episodes of focal with impaired awareness seizures. On examination, she had MMSE score of 8/30 and no motor weakness or abnormal reflexes. She was evaluated for her symptoms.ResultMRI showed elongated curvilinear altered signal intensity structure consistent with fat at inter‐hemispheric fissure, pericallosal in location, adjacent to body, isthmus and splenium of corpus callosum indicating pericallosal lipoma (curvilinear type).ConclusionPericallosal lipoma is a rare congenital malformation of brain that can be associated with dysgenesis or agenesis of the corpus callosum. It is usually asymptomatic, but can manifest with seizures, dementia, paralysis or headaches. CT and MR imaging play an important role in making this diagnosis.

EEG networks from the agenesis of corpus callosum and epilepsy

EEG networks from the agenesis of corpus callosum and epilepsy

Congenital Zika Virus Infection Impairs Corpus Callosum Development.

Congenital Zika syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with a Brazilian ZIKV isolate and found that they were born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction in PH3+ cells, intermediate progenitor cells, and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV-infected cultures show a reduction in callosal axon length. GFAP labeling showed that an in utero infection compromises glial cells responsible for midline axon guidance. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis, but also axon guidance and growth across the midline.

Prenatal Magnetic Resonance Imaging helps Discover Cerebellar Dysplasia or Malformations in Foetuses.

This study aimed to characterize and assess the diagnostic value of prenatal magnetic resonance (MR) imaging in detecting fetal cerebellar hypoplasia/dysplasia and developmental malformations. Reports of suspected intracranial abnormalities were retrospectively collected on ultrasound screening (US), and MR images of fetuses were reviewed at our institution over a 5-year period on picture archiving and communication system (PACS) servers. Two experienced radiologists recorded major abnormalities and coexisting abnormalities at the reading of the census. The results of the MRI were compared against the US in each case. For prenatal MR imaging, we enlisted a total of 121 patients (mean gestational week, 24.5 ± 4.7 weeks). This included 28 cases with normal findings of MR imaging, 62 cases with findings of cerebellar hypoplasia or dysplasia, and the remaining 31 cases with other abnormities findings. Cerebral malformations cases included agenesis of the corpus callosum, cerebral hemorrhage, hydrocephalus, holoprosencephaly, ventriculomegaly, and brainstem/gyri malformation. Cerebellar abnormalities included vermis absence, cerebellar tonsil hernia, Dandy-Walker malformation, Blake's pouch cysts, arachnoid cysts, and intracranial hemorrhage. Other systemic malformation cases included tethered cord syndromes (9 cases), cleft lip and palate (1 case), club foot (1 case), and cardiac malformation (1 case). In 12 cases (24.5%), compared to the US, MR imaging proved the value of confirming the diagnosis and/or even yielded more findings on abnormalities. Prenatal MR imaging can better visualize systemic malformations coexisting with cerebellar abnormalities. MR imaging, a complementary means to the US, can aid in prenatal counseling and treatment selection for term delivery.

NUP85 as a Neurodevelopmental Gene: From Podocyte to Neuron.

Pathogenic gene variants encoding nuclear pore complex (NPC) proteins were previously implicated in the pathogenesis of steroid-resistant nephrotic syndrome (SRNS). The NUP85 gene, encoding nucleoporin, is related to a very rare form of SRNS with limited genotype-phenotype information. We identified an Italian boy affected with an SRNS associated with severe neurodevelopmental impairment characterized by microcephaly, axial hypotonia, lack of achievement of motor milestones, and refractory seizures with an associated hypsarrhythmic pattern on electroencephalography. Brain magnetic resonance imaging (MRI) showed hypoplasia of the corpus callosum and a simplified gyration of the cerebral cortex. Since the age of 3 years, the boy was followed up at our Pediatric Nephrology Department for an SRNS, with a focal segmental glomerulosclerosis at renal biopsy. The boy died 32 months after SRNS onset, and a Whole-Exome Sequencing analysis revealed a novel compound heterozygous variant in NUP85 (NM_024844.5): 611T>A (p.Val204Glu), c.1904T>G (p.Leu635Arg), inherited from the father and mother, respectively. We delineated the clinical phenotypes of NUP85-related disorders, reviewed the affected individuals so far reported in the literature, and overall expanded both the phenotypic and the molecular spectrum associated with this ultra-rare genetic condition. Our study suggests a potential occurrence of severe neurological phenotypes as part of the NUP85-related clinical spectrum and highlights an important involvement of nucleoporin in brain developmental processes and neurological function.

Septo-Optic Dysplasia: A Case Series of 33 Patients

ABSTRACT The objective of this study was to record the clinical, neuro-radiological, and systemic features of patients with septo-optic dysplasia (SOD). A retrospective review of patients was conducted to identify patients with features consistent with SOD over a 6-year period, including optic nerve hypoplasia with agenesis of midline structures, along with an absent septum pellucidum and/or agenesis of the corpus callosum. Thirty-three patients were identified. The male to female ratio was 2:1, while the median age at diagnosis was 5 years (interquartile range = 10 years, range = 0–44 years). Optic nerve hypoplasia (ONH) was bilateral in 81.81% of cases (n = 27) and unilateral in 18.18% of cases (n = 6), with three cases in each eye. Developmental delay was documented in 24.2% (n = 8). The most frequent magnetic resonance imaging features that were consistent with SOD included: isolated absent septum pellucidum reported in 51.51% (n = 17); isolated corpus callosum agenesis in 33.33% (n = 11); and both absent septum pellucidum and corpus callosum agenesis in 15.15% (n = 5). Pituitary gland abnormalities, including pituitary hypoplasia in 9% (n = 3) or hypoplasia of pituitary infundibulum in 6% (n = 2) were less common. Pituitary hormonal abnormalities were present in 50% of the 10 tested patients (n = 5). Although bilateral ONH is more frequent, hypoplasia of just one optic nerve could be a presenting feature of SOD. Therefore, additional neuro-imaging is important for a diagnosis in cases of unilateral and bilateral ONH and a multidisciplinary approach is beneficial.

Anomalies of the Corpus Callosum in Prenatal Ultrasound: A Narrative Review for Diagnosis and Further Counseling.

The corpus callosum is the major interhemispheric tract that plays an important role in neurological function. Understanding the etiology and embryology development helps the ultrasound diagnosis for disorders of the corpus callosum and further counseling. The nonvisualization of cavum septum pellucidum or dysmorphic cavum septum pellucidum in axial view are indirect signs for beginners to diagnose complete agenesis of corpus callosum (cACC) and partial agenesis of the corpus callosum (pACC). Further coronal view, sagittal view, and fetal magnetic resonance imaging are also important for evaluation. Genetic testing plays an essential tool in anomalies of corpus callosum by revealing the underlying genetic pathophysiology, such as chromosomal anomalies and numerous monogenetic disorders in 30%-45% of ACC. Diagnosis and prediction of prognosis for hypoplasia or hyperplasia of the corpus callosum are more difficult compared to cACC and pACC because of the limited reports in the literature. However, the complex types often had poorer prognostic outcomes compared to the isolated types. Hence, it is important to evaluate and follow fetal conditions thoroughly to rule out intracranial or extracranial anomalies in other systems.

Threat and adaptation: The maternal lived experience of continuing pregnancy after receiving a prenatal diagnosis of agenesis of the corpus callosum

One stated objective of prenatal screening and diagnosis is the preparation for delivering a baby with medical needs or disability, however, psychosocial outcomes of parents who received a prenatal diagnosis suggest that this objective is not yet realised. Preparation may be complicated by diagnostic and prognostic uncertainty. A prenatal diagnosis that includes significant uncertainty due to the heterogeneous presentations, classifications, causes and outcomes is agenesis of the corpus callosum. As a neuroanatomical anomaly identified in the second or third trimesters, the diagnosis is likely to cause distress for expectant mothers, yet there is limited guidance for holistic support. To begin to address the paucity of research, this hermeneutic phenomenological study sought to explore, and provide a telling of the maternal experience of continuing pregnancy after a prenatal diagnosis of agenesis of the corpus callosum. Through interviews and a series of online, asynchronous and facilitated focus groups, lived experiences during pregnancy from the time of diagnosis to birth were explored with 26 mothers who participated in this international study. Themes were constructed through reflexive thematic analysis to describe the experience of the lived phenomenon. The first theme, Under Threat, included subthemes of The Threat to the Life of the Baby and Threatened Image of the Expected Family. The second theme, Day to Day Toward Adaptation, included subthemes of Holding it Together and Falling Apart, and More Than Information, Searching for Meaning, Hope and Control. To realise the commonly stated objective of prenatal diagnosis, to support maternal preparation, healthcare professionals require awareness of the profound, yet individual experience of prenatal diagnosis to adequately respond and support mothers through their continued pregnancies. Healthcare services should be designed to flexibly respond in a woman- and family-centred manner to reduce the threat and support maternal adaptation after a prenatal diagnosis.

Brain plasticity following corpus callosum agenesis or loss: a review of the Probst bundles.

The corpus callosum is the largest axonal tract in the human brain, connecting the left and right cortical hemipheres. This structure is affected in myriad human neurodevelopmental disorders, and can be entirely absent as a result of congenital or surgical causes. The age when callosal loss occurs, for example via surgical section in cases of refractory epilepsy, correlates with resulting brain morphology and neuropsychological outcomes, whereby an earlier loss generally produces relatively improved interhemispheric connectivity compared to a loss in adulthood (known as the "Sperry's paradox"). However, the mechanisms behind these age-dependent differences remain unclear. Perhaps the best documented and most striking of the plastic changes that occur due to developmental, but not adult, callosal loss is the formation of large, bilateral, longitudinal ectopic tracts termed Probst bundles. Despite over 100 years of research into these ectopic tracts, which are the largest and best described stereotypical ectopic brain tracts in humans, much remains unclear about them. Here, we review the anatomy of the Probst bundles, along with evidence for their faciliatory or detrimental function, the required conditions for their formation, patterns of etiology, and mechanisms of development. We provide hypotheses for many of the remaining mysteries of the Probst bundles, including their possible relationship to preserved interhemispheric communication following corpus callosum absence. Future research into naturally occurring plastic tracts such as Probst bundles will help to inform the general rules governing axon plasticity and disorders of brain miswiring.

3 The Aesthetics of Empathy in Agenesis of the Corpus Callosum

Objective:Previous research suggests that individuals with isolated Agenesis of the Corpus Callosum (AgCC) have cognitive and psychosocial deficiencies that include impaired recognition of the emotions of others (Symington et al., 2010) and a diminished ability to infer and describe the emotions of others (Paul et al., 2021; Turk et al., 2010). In addition, galvanic skin responses effectively discriminated between emotional images despite atypical emotion ratings (Paul et al, 2006), supporting a dissociation between cognitive and affective empathy in AgCC. Likewise, atypical patterns of visual attention to faces corresponded with impaired emotion recognition in AgCC (Bridgman et al, 2014), suggesting that atypical visual attention in AgCC negatively impacts the ability to identify others’ emotions. This study used the Multifaceted Empathy Test [MET] (Foell et al., 2018) to examine the impact of visual aesthetics (photo composition) on empathetic feelings (affective empathy) and situational emotion recognition (cognitive empathy) in persons with AgCC. Both cognitive and affective empathy scores are typically higher on MET stimuli composed according to the “Golden Spiral” (Callaway, 2022).Participants and Methods:Results from 50 control participants recruited from Cloud Research were compared to responses from 19 participants with AgCC and normal-range FSIQ (>80). Data was gathered through an online version of the MET, which uses a series of photographs of individuals displaying an emotion, half of which adhere to the compositional technique known as “The Golden Spiral.” To measure cognitive empathy, the participants are asked to pick the correct emotion being displayed with three distractors for each item. To measure affective empathy, they are then asked on a sliding scale, “how much do you empathize with the person shown” (1 = Not at all, 7 = Very much).Results:Repeated measures mixed ANOVAs revealed no difference between AgCC and control groups on affective empathy, and as expected on the MET, both groups had significantly higher ratings for photos composed according to the Golden Spiral (AgCC, np2 = .071; control, np2 = .136). In contrast, the AgCC group scored significantly lower than controls overall on cognitive empathy, np2 =.065. Exploratory post-hoc found a significant group difference in cognitive empathy only on photos composed according to the Golden Spiral, np2 = .090, with the scores in the AgCC group unimpacted by composition type while the control group exhibiting significantly higher scores Golden Spiral images, np2 = .254.Conclusions:Empathic deficits in AgCC were restricted to the cognitive component, while affective empathy was not impaired. Visual aesthetics of photo composition influenced affective empathy ratings in both AgCC and control groups. However, adults with AgCC had diminished ability to give cognitive labels to the emotional states of others, which was not enhanced by the formal aesthetics of stimuli. Thus the corpus callosum seems to facilitate the ability to cognitively label emotions by facilitating visual attention. It also suggests that the corpus callosum does not facilitate affective empathy, in part because it does not appear to determine whether formal aesthetics influences the processing of visual stimuli in AgCC or neurotypical controls.

39 Empathic Abilities of Individuals with Agenesis of the Corpus Callosum

Objective:Previous research suggests that individuals with isolated Agenesis of the Corpus Callosum (AgCC) have cognitive and psychosocial deficits including that of complex processing of emotions (Anderson et al., 2017) and their ability to verbally express emotional experiences (Paul et al., 2021). Additionally, research suggests individuals with AgCC show impaired recognition of the emotions of others (Symington et al., 2010), as well as diminished ability to infer and describe the emotions of others (Renteria-Vazquez et al., 2022; Turk et al., 2010). However, the nature of the empathic abilities of individuals with AgCC remains unclear in empirical research. Capacity for empathetic feelings and situational recognition in persons with AgCC were tested using the Multifaceted Empathy Test [MET] (Foell et al., 2018). We hypothesized that individuals with AgCC would have lower abilities for both cognitive and affective empathy than neurotypical controls.Participants and Methods:Results from 50 neurotypical control participants recruited from MTurk Cloud were compared to responses from 19 AgCC participants with normal-range FSIQ (>80) drawn from the individuals with AgCC involved with the Human Brain and Cognition Lab at the Travis Research Institute. The research was completed through an online version of the MET. The MET uses a series of photographs of individuals displaying an emotion. To measure cognitive empathy, the participants are asked to pick the correct emotion being displayed with three distractors for each item. To measure affective empathy, they are then asked on a sliding scale, “how much do you empathize with the person shown” (1 = Not at all, 7 = Very much).Results:Results of a MANOVA showed a trend for a significant overall difference between individuals with AgCC and controls for empathic abilities F(1, 67) = 2.59, p-value = .082, with persons with AgCC showing less empathy overall. Follow-up one-way ANOVAs showed that individuals with AgCC scored significantly lower in cognitive empathy F(1, 67) = 4.63, p-value = .035, ηp2 = .065; however, affective empathy was not significantly different between groups F(1, 67) = .537, p-value = .466, ηp2 = .008.Conclusions:Results suggest that adults with AgCC have a diminished ability to give cognitive labels to the emotional states of others compared to neurotypical controls. However, contrary to our hypothesis, participants with AgCC had affective responses to the pictures of the emotional states of others which were similar to neurotypical controls. Recent research has shown that individuals with AgCC have difficulty inferring and elaborating on the more complex cognitive, social, and emotional aspects of simple animations (Renteria-Vazquez et al., 2022; Turk et al., 2010). Cognitive empathy would require this form of elaborative thinking, even when affective empathy is normal. Similarly, Paul et al. (2021) described alexithymia in persons with AgCC as difficulty in expressing emotions linguistically, but found similar endorsements of emotional experience when compared to neurotypical controls. This study provides further evidence to suggest the corpus callosum facilitates the ability to cognitively label emotions but not necessarily the ability to experience emotions affectively.

2 Musical perception skills in Agenesis of the Corpus Callosum

Objective:Agenesis of the corpus callosum(AgCC) is a disorder in which the connection between the two brain hemispheres is congenitally absent. Previous research has suggested that the auditory system can be affected in individuals with AgCC (Demopoulos et al., 2015). However, the nature of AgCC’s effect on musical perception skills is unclear. This study investigated the impact of AgCC on the music perception skills in high-functioining adults using a brief version of the Profile of Music Perception Skills (PROMS; Zentner, M. & Strauß, H. 2017). It was hypothesized that individuals with AgCC would have diminished music perception abilities when compared to a neurotypical control group.Participants and Methods:Participants included 10 high-functioning adults with AgCC that had an intelligence quotation within the normal range (FSIQ>80) and 63 neurotypical controls who were recruited via Cloud Research. During the PROMS the participants were asked to listen to two different sound excerpts after which they were asked whether the second sound was the same or different from the first (correct answers= 2 points, uncertain answers= 1 point, and remaining answers not coded). The participants answered questions in four different areas of musical perception: Melody, Tuning, Accent, and Tempo.Results:Results indicated that there was not a significant difference between the control group and the AgCC participants on music perception skills on the overall PROMS scores F(1,72)= .365, P-value= .548. Tested individually, none of the 4 individual domains showed a significant difference: Melody F(1,72)=2.67, P-value= .107; Tuning F(1,72)= .271, P-value= .606; Accent F(1,72)= .017, P-value= .897; or Tempo F(1,72)=.106, P-value= .746.Conclusions:Contrary to the hypothesis of this study, the results showed that the participants with AgCC did not perform significantly differently in the PROMS total score when compared to neurotypical controls, nor were there significant differences in any of the four of the subtests (Melody, Tuning, Accent, and Tempo). Thus these high-functioning individuals with AgCC did not have deficient music perception abilities. These findings demonstrate that although the auditory system may be affected in some individuals with AgCC, we do not see differences in musical perception skills in high-functioning individuals with AgCC.

1 Moral Reasoning in Individuals with Agenesis of the Corpus Callosum

Objective:Previous research has demonstrated that individuals with Agenesis of the Corpus Callosum (AgCC), the congenital absence of all or part of the corpus callosum, exhibit a pattern of cognitive and psychosocial deficits, even with a FSIQ in the normal range (FSIQ > 80; Brown & Paul, 2019). This includes a core deficit in their complex reasoning and novel problem-solving (Brown & Paul, 2019), with secondary deficits in capacity to imagine complex emotional/cognitive consequences of potential actions involving others (Young et al, 2019), deficits in emotionperception (Symington et at., 2010, Bridgman et al 2014), and difficulty with cognitively processing emotions within the context of social interactions (Anderson et al., 2017). This constellation of deficits is likely to also impact moral reasoning. While previous research has demonstrated differences in moral reasoning among other neuropsychological populations such as those with ventromedial prefrontal damage (Moretto et al., 2010) and frontotemporal dementia (Gleichgerrcht et al., 2011), there is no research reported regarding moral judgements in AgCC. This study employed the Moral Dilemmas Scale (Greene, 2001) to compare the moral judgements of persons with AgCC to neurotypical controls. It was predicted that individuals with AgCC would be less contextually nuanced than neurotypical controls in responding to moral dilemmas.Participants and Methods:Results consist of data derived from 57 neurotypical control participants (ages 23 to 64 years) recruited from MTurk Cloud and 19 AgCC participants (ages 23 to 77 years) with normal-range FSIQ (>80) drawn from the individuals with AgCC involved with the Human Brain and Cognition Lab at the Travis Research Institute. All participants completed an online version of the Moral Dilemmas Scale (Greene, 2001). The scale consists of 25 dilemmas, of which 11 are considered high-conflict, 7 low-conflict and 7 impersonal. Participants were instructed to read each dilemma and rate whether they found the action to be “appropriate” or not. The high-conflict dilemmas share a similar structure in which responses reflect either a utilitarian or deontological judgement.Results:“Approve” responses to each of the 3 categories of dilemma were separately tallied for each individual and subjected to a 2group ANOVA. Results revealed the control group produced a significantly higher rate of “appropriate” responses to high-conflict dilemmas than did the individuals with AgCC (F=8.17, p = .006, n2 =.113). However, no significant differences were found among the two groups for results on low (n2 = .013) and impersonal (n2 = .003) dilemmas alone. Furthermore, a X2 analysis of responses to each high conflict dilemma revealed a significant difference in 5 out of the 11 such that more persons with AgCC gave a deontological judgement.Conclusions:Results suggested that adults with AgCC respond similarly to neurotypical controls with respect to the low conflict orimpersonal dilemmas. However, with respect to high conflict dilemmas, compared to controls they tend to respond in a more deontological than utilitarian basis - that is, based on general principles without contextual nuance. These findings are consistent with the conclusion of Renteria-Vasquez et al. (2021) that persons with AgCC have difficulty imagining the wider implications of present information.

2 Early Presentation of Autistic Features in Infants with Agenesis of the Corpus Callosum

Objective:Agenesis of the Corpus Callosum (ACC), a congenital disorder in which the corpus callosum partially or completely fails to develop properly, occurs in ∼1 in 4,000 live births. ACC has been identified as a major risk factor for receiving an Autism Spectrum Disorder (ASD) diagnosis (∼10% diagnosis rate, as compared to 2.3% in the general population), but little is currently known about behavioral and social development during infancy and early childhood in this disorder. In this study we aim to 1) characterize the manifestation of autistic features in 24-month-old children (a common age for early diagnosis of ASD) with ACC and a convenience sample of age matched comparison children from the community, and 2) determine if parent reports of autistic features during the first year of life are associated with reciprocal social behavior and autistic traits at 24-months of age in children with ACC.Participants and Methods:Parents of infants who had received a diagnosis of ACC completed the Parent Rating of Communication, Emotion, and Social Skills (PROCESS) for their child at 6, 12, and 24-months of age, and the video-referenced rating of reciprocal social behavior (vrRSB) at 24-months of age. Comparison data were obtained from a convenience community sample in Minnesota. Aim 1). The distributions of PROCESS total scores at 24-months were compared between the ACC group (n=43) and control group (n=1058) via a 2-tailed t-test. Likewise, distributions of reciprocal social behavior (RSB) scores at 24 months were compared between ACC (n=72) and controls (n=1438) via a 2-tailed t-test. Aim 2). A partial Pearson Correlation was conducted between ACC participants’ 6-month PROCESS scores and 24-month RSB (n=18) scores, as well as between their 12-month PROCESS and 24-month vrRSB (n=37) scores, controlling for child sex.Results:Aim 1). At 24 months of age, children with ACC are reported to have significantly higher PROCESS scores (t = 3.73, df = 42.67, p < .001), and RSB (t = 4.89, df = 88.38, p < .001) scores than comparison toddlers, indicating an elevated presentation of behaviors associated with autistic features. Aim 2). No correlation was found between participants’ 6-month PROCESS and 24-month RSB scores (r(16) = .39, p = .12). A relatively strong correlation (r(35) = .60, p < .001) was found between participants’ 12-month PROCESS and 24-month RSB scores.Conclusions:As early as two years of age, children with ACC display a heightened presentation of autistic features compared to typically developing controls. Additionally, reports of social behaviors related to ASD at 24-months are correlated with reports of autistic features at 12-months of age. This evidence indicates that children with ACC who are at a higher likelihood for being diagnosed with ASD may be identified as early as 12-months old. Formulating and leveraging an early identification methodology is imperative for this population with an already elevated risk for ASD, as providing early interventions leads to improved outcomes later in life.

Symposium 07: Early Development in Infants and Toddlers with Agenesis of the Corpus Callosum

Summary AbstractThe corpus callosum is the largest transverse white matter fiber tract connecting the two hemispheres of the brain. It plays an essential role in the interhemispheric transfer and bihemispheric coordination involved in perception and sensory-motor integration, as well as higher level cognition (e.g., memory, executive functioning). The corpus callosum forms prenatally (10-15 weeks gestation) and continues to develop through early adulthood. Damage to the corpus callosum throughout the lifespan, but especially later in life, can result in sensory and motor coordination deficits and produces disconnection syndromes.However, individuals born with a partial or fully absent corpus callosum, known as Agenesis of the Corpus Callosum (ACC), do not exhibit a full disconnection syndrome and may, in fact, demonstrate many intact skills including broadly average intellectual abilities. Agenesis of the corpus callosum (ACC) is a relatively common congenital brain malformation that occurs in 1 out of ∼4000 live births (Glass, Shaw, Ma, & Sherr, 2008; Paul et al., 2007). There is significant heterogeneity in outcomes for these individuals, often related to the presence of additional neuropathology, and the presence of co-occurring medical and genetic conditions. In adults for whom ACC is the primary neurological finding, there is a core constellation of cognitive symptoms that include reduced interhemispheric transfer, slowed processing, and difficulty with complex novel problem solving (Brown & Paul, 2019). There is also an elevated likelihood of autism spectrum disorders in this population as well (Paul et al, 2014).Modern ultrasound technology facilitates diagnosis of ACC in utero, offering a unique opportunity to study these individuals’ development from infancy. However, no studies to date have examined early development in this population using validated measures, leaving neuropsychologists, neurologists and primary care providers to make educated guesses about what families should expect and appropriate therapies/treatment.This symposium presents a series of studies examining the early development of individuals with primary ACC across domains including language, adaptive skills, autism symptomology, and temperament/anxiety. We will provide the first in-depth prospective characterization of development in ACC relative to typically developing children at 6, 12, 18 and 24 months and discuss what these findings reveal about brain development and plasticity more broadly (e.g. how does early disruption in interhemispheric connection impact cognitive development across key domains?).Finally, while ACC is defined specifically by corpus callosum anatomy, the corpus callosum has been implicated in other neurodevelopmental conditions (Paul, 2011). Utilizing extant comparison, we also assess how early development in ACC both overlaps and differs from two monogenic conditions (e.g. Fragile X and Down Syndrome) and a developmental behavioral diagnoses (e.g. autism) and discuss how early disruptions in interhemispheric transfer may contribute to shared behavioral phenotypes in these conditions.

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.

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.

1 Early Development of Adaptive Skills in Young Children with Agenesis of the Corpus Callosum: A Comparison to Monogenetic and Neurodevelopmental Conditions

Objective:Differences in adaptive functioning present early in development for many children with monogenic (Down Syndrome, Fragile X) and neurodevelopmental disorders. At this time, it is unclear whether children with ACC present with early adaptive delays, or if difficulties emerge later as functional tasks become more complex. While potential delays in motor development are frequently reported, other domains such as communication, social and daily living skills are rarely described. We used a prospective, longitudinal design to examine adaptive behavior from 6-24 months in children with ACC and compared their trajectories to those with monogenic and neurodevelopmental conditions.Participants and Methods:Our sample included children with primary ACC (n= 27-47 depending on time point) whose caregivers completed the Vineland Adaptive Behavior Scales-Interview 3rd Edition, via phone at 6, 12, 18 and 24 months. Comparison samples (using the Vineland-2) included children with Down Syndrome (DS; n = 15-56), Fragile X (FX; n = 15-20), children at high familial likelihood for autism (HL-; n=192-280), and low likelihood (LL; no family history of autism and no developmental/behavioral diagnosis; n = 111196). A subset of the HL children received an autism diagnosis (HL+; n = 48-74). The DS group did not have an 18-month Vineland.Results:A series of linear mixed model analyses (using maximum likelihood) for repeated measures was used to compare groups on three Vineland domains at 6, 12, 18 and 24 month timepoints). All fixed factors (diagnostic group, timepoint, and group X timepoint interaction) accounted for significant variance on all Vineland domains (p < .001). Post hoc comparisons with Bonferroni-correction examined ACC Vineland scores compared to the other diagnostic groups at each timepoint. At 6 months, parent-ratings indicated the ACC group had significantly weaker skills than the LL group in Communication and Motor domains. At 12, 18 and 24 months, ratings revealed weaker Communication, Daily Living and Motor skills in the ACC group compared to both the LL and HL- groups. Compared to the other clinical groups, the ACC group had stronger Socialization and Motor skills than Fragile X at 6 months, and at 24 months had stronger Communication and Socialization skills than both the DS and FX groups, as well as stronger Socialization than the HL+ group.Conclusions:Compared to children with low likelihood of ASD, children with primary ACC reportedly have weaker Communication and Motor skills from 6 to 24 months, with weakness in Daily Living Skills appearing at 12 months and all differences increase with age. Compared to Fragile X, the ACC exhibited relative strengths in socialization and motor skills starting at 6 months. By 24 months, the ACC group was outperforming the monogenic groups on Socialization and Communication. In general, the ACC scores were consistent with the HL+ sample, except the ACC group had stronger Social skills at 18 and 24 months. The results clearly inform the need for early intervention in the domains of motor and language skills. Additionally, as we know that children with ACC are at increased risk for social difficulties, research is needed both using more fine-grained social-communication tools, and following children from infancy through middle childhood.

Clinicoradiological Profile of Incomplete Hippocampal Inversion Diagnosed on MR Neuroimaging.

Incomplete hippocampal inversion (IHI) is a developmental failure of normal hippocampal inversion. Previous studies have described IHI in epilepsy and non-epilepsy subjects. IHI has also been reported with malformations of cortical development (MCDs) and corpus callosal agenesis that have association with neuropsychiatric disorders such as autism spectrum disorder (ASD). This study aims to describe the clinical profile of magnetic resonance imaging (MRI)-diagnosed IHI. We studied patients with IHI who were identified after a retrospective review of the MRI archives of the past 3 years. The MRI findings of partial and total IHI were included. The clinical profiles associated with IHI were classified into epilepsy and non-epilepsy categories. A retrospective review of MRI done over 3 years revealed 54 cases of IHI (32 left-sided, 20 bilateral, and 2 isolated right-sided), and out of 74 IHI, 59 were of total type and 15 partial. Thirty-six subjects (61.1%) had epilepsy (9 with neurodevelopmental problems), 17 subjects (31.5%) had ASD, and 4 subjects (7.4%) had only neurodevelopmental disorders. MCDs were seen in 7 (12.9%): polymicrogyria (4), periventricular heterotopia (2), and pachygyria (1). Hippocampal volume loss was seen in 10, and contralateral mesial temporal sclerosis was seen in 2 patients. Hippocampal inversion has been reported in MRI scans of patients with epilepsy, ASD, MCDs, and many other related disorders. Further studies are required to know its occurrence among patients who get MRI scans due to many other disorders such as headaches, psychiatric disorders, minor hear trauma, and perinatal insults. If possible, studies among normal populations also need to be done.