Isolated Agenesis Of Corpus Callosum Research Articles

Developmental surface dyslexia and dysgraphia in a child with corpus callosum agenesis: an approach to diagnosis and treatment

ABSTRACT We present a case study detailing cognitive performance, functional neuroimaging, and effects of a hypothesis-driven treatment in a 10-year-old girl diagnosed with complete, isolated corpus callosum agenesis. Despite having average overall intellectual abilities, the girl exhibited profound surface dyslexia and dysgraphia. Spelling treatment significantly and persistently improved her spelling of trained irregular words, and this improvement generalized to reading accuracy and speed of trained words. Diffusion weighted imaging revealed strengthened intrahemispheric white matter connectivity of the left temporal cortex after treatment and identified interhemispheric connectivity between the occipital lobes, likely facilitated by a pathway crossing the midline via the posterior commissure. This case underlines the corpus callosum’s critical role in lexical reading and writing. It demonstrates that spelling treatment may enhance interhemisphericconnectivity in corpus callosum agenesis through alternative pathways, boosting the development of a more efficient functional organization of the visual word form area within the left temporo-occipital cortex.

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.

The ultrasound evaluation of corpus callosum in the routine screening is not recommended, because we know less than we see

The corpus callosum serves as a link between the two hemispheres, with an important role in cognitive mechanisms, also integrating motor and sensitive information and processing stimuli. Evaluation of the morphologic structure of the corpus callosum in order to diagnose structural anomalies such as hyperplasia, hypoplasia, as well as indirect signs of corpus callosum agenesia can be realised using ultrasonography during the mid-trimester screening. At present, it is recommended to perform a targeted evaluation only in high-risk cases of central nervous system abnormalities; the International Society of Ultrasound in Obstetrics and Gynaecology has not included the corpus callosum evaluation in the routine second trimester screening. Callosal anomalies present uncertainty in the fetal prognosis: 75% of cases of isolated corpus callosum agenesis develop normally; on the other hand, they could develop various degrees of neurological impairment from language or social deficiency to autism or schizophrenia. We, therefore, highlight the importance of corpus callosum evaluation, as the agenesis of the corpus callosum can be an isolated defect, but it can also be associated with other extracerebral anomalies or it could be a part of a syndrome. Completing the diagnosis often requires magnetic resonance imaging and genetic tests.

Visual System Abnormalities in a Case of Nonsyndromic, Complete, Isolated Corpus Callosum Agenesis.

Barbano, Lucilla MD; Ziccardi, Lucia MD, PhD; Antonelli, Giulio MD; Tinelli, Emanuele MD, PhD; Parisi, Vincenzo MDEditor(s): Avery, Robert DO; Golnik, Karl C. MD; Froment, Caroline MD, PhD; Wang, An-Guor MD Author Information

Long-term follow-up in a cohort of children with isolated corpus callosum agenesis at fetal MRI.

ObjectiveThis long‐term retrospective follow‐up study aimed to address the knowledge gap between prenatal diagnosis of complete isolated Agenesis of Corpus Callosum (cACC) at fetal MRI and postnatal neurodevelopmental outcome to improve prenatal counseling for parents.MethodsData on fetuses with isolated cACC from a single‐center MRI database built up in two decades were considered. Detailed postnatal clinical, neuropsychological evaluations were performed and descriptions of available neuroradiological and genetic data were provided.ResultsFollowing a detailed neuropsychological evaluation and a long‐term follow‐up, the subsequent results emerged: 38 school‐aged children (older than 6 years) of 50 (aged 2.5‐15 years) showed normal intellectual functions (50%), intellectual disability (21%), and borderline intelligence quotient (29%). Deficits in motor functions (58%), executive functions (37%), language (61%), memory abilities (58%), and academic performances (53%) were found. Twenty‐one percent of participants showed behavioral difficulties. Almost half of the participants underwent rehabilitation. Additional findings (21%) were detected at postnatal brain MRI, and a significant association between additional findings at postnatal imaging and abnormal neurodevelopmental outcome was observed.InterpretationsThis study supports the view that children with prenatal diagnosis of isolated cACC may present with several degrees of neurologic and neuropsychological impairment which become more evident only in their second decade of life. Postnatal MRI and detailed genetic analysis may add crucial information to prenatal data and substantially influence final judgment on the outcome and orient clinical management and counseling.

Beyond Isolated and Associated: A Novel Fetal MR Imaging-Based Scoring System Helps in the Prenatal Prognostication of Callosal Agenesis.

Although "corpus callosum agenesis" is an umbrella term for multiple entities, prenatal counseling is based reductively on the presence (associated) or absence (isolated) of additional abnormalities. Our aim was to test the applicability of a fetal MR neuroimaging score in a cohort of fetuses with prenatally diagnosed isolated corpus callosum agenesis and associated corpus callosum agenesis and correlate it with neurodevelopmental outcomes. We performed a single-center retrospective analysis of a cohort of cases of consecutive corpus callosum agenesis collected between January 2011 and July 2019. Cases were scored by 2 raters, and interater agreement was calculated. Outcome was assessed by standardized testing (Bayley Scales of Infant and Toddler Development, Kaufman Assessment Battery for Children) or a structured telephone interview and correlated with scores using 2-way ANOVA. We included 137 cases (74 cases of isolated corpus callosum agenesis), imaged at a mean of 27 gestational weeks. Interrater agreement was excellent (0.98). Scores were higher in associated corpus callosum agenesis (P < .0001) without a significant score difference between complete and partial corpus callosum agenesis (P = .38). Outcome was assessed in 42 children with isolated corpus callosum agenesis and 9 with associated corpus callosum agenesis (mean age, 3.1 years). MR imaging scores correctly predicted developmental outcome in 90.7% of patients with isolated corpus callosum agenesis, improving neurodevelopmental risk stratification in corpus callosum agenesis. The scoring system is very reproducible and can differentiate isolated corpus callosum agenesis and associated isolated corpus callosum agenesis (significantly higher scores) but not between partial and complete corpus callosum agenesis. Scores correlated with outcome in isolated corpus callosum agenesis, but there were too few associated postnatal cases of isolated corpus callosum agenesis to draw conclusions in this group.

Does fetal MR alter the management of pregnancy in the diagnosis of isolated corpus callosum agenesis?

Objective To determine if fetal MR alters the management of pregnancy and family decisions in the isolated corpus callosum agenesis (CCA) cases or not. Methods Fetal MR was carried out in the cases diagnosed with CCA in the Perinatology Unit of our hospital between 2013 and 2019 after they were differentiated as complex and isolated CCA cases. The impact of MR results on the family decisions and their approaches towards termination were assessed. Results A total of 109 out 139 cases were evaluated as isolated CCA. While 93 (85.32%) of them were diagnosed with the complete CCA, 16 (14.68%) cases were diagnosed with the partial CCA. When the period after 2017 during which fetal MR was recommended to all patients was reviewed, it was seen that 7 (23.3%) of 30 cases who underwent fetal MR and 2 (20%) of 10 cases who did not undergo fetal MR terminated their pregnancies. There was no statistical difference between two groups in terms of the decisions of the patients for gestational termination who did and did not undergo fetal MR. Conclusion Fetal MR imaging in the isolated CCA does not change the decisions of the families for the gestational termination. In terms of the termination decision, week of gestation and socio-cultural factors may have more impacts.

Underdevelopment of the Human Hippocampus in Callosal Agenesis: An In Vivo Fetal MRI Study

In subjects with agenesis of the corpus callosum, a variety of structural brain alterations is already present during prenatal life. Quantification of these alterations in fetuses with associated brain or body malformations (corpus callosum agenesis and other related anomalies) and so-called isolated cases may help to optimize the challenging prognostic prenatal assessment of fetuses with corpus callosum agenesis. This fetal MR imaging study aimed to identify differences in the size of the prenatal hippocampus between subjects with isolated corpus callosum agenesis, corpus callosum agenesis and other related anomalies, and healthy controls. Eighty-five in utero fetal brain MR imaging scans, (20-35 gestational weeks) were postprocessed using a high-resolution algorithm. On the basis of multiplanar T2-TSE sequences, 3D isovoxel datasets were generated, and both hippocampi and the intracranial volume were segmented. Hippocampal volumes increased linearly with gestational weeks in all 3 groups. One-way ANOVA demonstrated differences in hippocampal volumes between control and pathologic groups (isolated corpus callosum agenesis: left, P = .02; right, P = .04; corpus callosum agenesis and other related anomalies: P < .001). Differences among the pathologic groups were also present for both sides. Intracranial volume and right and left hippocampal volume ratios were different between corpus callosum agenesis cases and controls (P < .001). When we corrected for intracranial volume, no differences were found between corpus callosum agenesis and other associated anomalies and isolated corpus callosum agenesis (left, P = .77; right, P = .84). Hippocampal size differences were more pronounced at a later gestational age. Callosal agenesis apparently interferes with the normal process of hippocampal formation and growth, resulting in underdevelopment, which could account for certain learning and memory deficits in individuals with agenesis of the corpus callosum in later life.

Counseling for Fetal Central Nervous System Defects

AbstractFetal central nervous system defects are one of the commonest antenatally detected abnormalities. They consist of a wide array of lesions with heterogeneous etiologies and outcomes. Counselling of the family in such cases forms an integral part of management. However, this can be challenging due to diagnostic and prognostic uncertainties for many defects. Some lesions like anencephaly, holoprosencephaly, and lissencephaly, have an invariably poor outcome, and decision regarding pregnancy termination is straightforward. On the other hand, lesions like mild ventriculomegaly, isolated corpus callosum agenesis and posterior fossa lesions have a highly variable outcome, ranging from normal to severe handicaps, hence counseling for these is difficult. Detailed sonography by an expert sonologist and fetal MRI can help in detection of additional cerebral or extracerebral abnormalities, which being associated with a poor prognosis, can help in accurate counseling. An often-neglected aspect of counseling is the possibility of recurrence in subsequent pregnancies, due to an underlying genetic etiology in many of these defects. This can be assessed by pedigree information, suitable genetic testing and postmortem examination in case of pregnancy termination. Diagnosis of the genetic abnormality helps in accurate recurrence-risk prediction as well as early and timely prenatal diagnosis in at-risk pregnancies.

Disrupted developmental organization of the structural connectome in fetuses with corpus callosum agenesis

Agenesis of the corpus callosum is a model disease for disrupted connectivity of the human brain, in which the pathological formation of interhemispheric fibers results in subtle to severe cognitive deficits. Postnatal studies suggest that the characteristic abnormal pathways in this pathology are compensatory structures that emerge via neural plasticity. We challenge this hypothesis and assume a globally different network organization of the structural interconnections already in the fetal acallosal brain.Twenty fetuses with isolated corpus callosum agenesis with or without associated malformations were enrolled and fiber connectivity among 90 brain regions was assessed using in utero diffusion tensor imaging and streamline tractography. Macroscopic scale connectomes were compared to 20 gestational age-matched normally developing fetuses with multiple granularity of network analysis.Gradually increasing connectivity strength and tract diffusion anisotropy during gestation were dominant in antero-posteriorly running paramedian and antero-laterally running aberrant pathways, and in short-range connections in the temporoparietal regions. In fetuses with associated abnormalities, more diffuse reduction of cortico-cortical and cortico-subcortical connectivity was observed than in cases with isolated callosal agenesis. The global organization of anatomical networks consisted of less segregated nodes in acallosal brains, and hubs of dense connectivity, such as the thalamus and cingulate cortex, showed reduced network centrality.Acallosal fetal brains show a globally altered connectivity network structure compared to normals. Besides the previously described Probst and sigmoid bundles, we revealed a prenatally differently organized macroconnectome, dominated by increased connectivity. These findings provide evidence that abnormal pathways are already present during at early stages of fetal brain development in the majority of cerebral white matter.

Isolated corpus callosum agenesis: a ten‐year follow‐up after prenatal diagnosis (How are the children without corpus callosum at 10 years of age?)

Corpus callosum agenesis (CCA) is generally diagnosed in utero. Outcome appears to be better if the malformation is isolated. The aim of this study, which is the first one with a long (10 years) and standardized follow up, was to report cognitive abilities of children with isolated CCA diagnosed prenatally. We prospectively evaluated 17 children. Clinical examinations, neuropsychological tests were performed each year. School achievement and personal and familial data were collected. Twelve children completed the entire follow up. One child was finally considered to have associated CCA, because signs of fetal alcohol syndrome had become obvious. Of the 11 other children, three (27%) had borderline intelligence whereas the intelligence levels of eight (73%) were in the normal range, although half of these children experienced some difficulties in scholastic achievement. Neither epilepsy nor intellectual deficiency was noted and intellectual quotient scores correlated strongly with the mother's education level. Although prenatal diagnosis of isolated CCA is reliable, false postnatal diagnoses remain possible (10-20%) even with complete prenatal screening. Outcome is mostly favorable because intelligence is within the normal range for nearly 3/4 of the children. However, they frequently have mild learning difficulties.

Isolated corpus callosum agenesis as a rare differenzial diagnosis of attention defficit hyperactivity disorder- case report

Isolated corpus callosum agenesis as a rare differenzial diagnosis of attention defficit hyperactivity disorder- case report

Assessment of Sulcation of the Fetal Brain in Cases of Isolated Agenesis of the Corpus Callosum Using In Utero MR Imaging

There is gathering evidence to suggest that agenesis of the corpus callosum is associated with delayed fetal sulcation; it is possible that the corpus callosum facilitates normal gyral development. In this paper we sought to confirm whether delayed sulcation is found in fetuses with isolated agenesis of the corpus callosum as judged by in utero MR imaging. Retrospective analysis of 20 fetuses with isolated corpus callosum agenesis investigated by in utero MR imaging and 20 aged-matched normal fetuses was performed in the second or third trimester. All fetuses were singleton pregnancies with known gestational age, imaged on a 1.5T superconducting MR system. Estimation of sulcation maturity was made with reference to a standard atlas and subgroup analysis of earlier gestation (group 1, 21-26 weeks) and later gestation (group 2, 30-34 weeks) fetuses was performed. Group 1 (n = 12) did not show a statistically significant difference between the 2 subgroups (P = .44) in terms of sulcation. A significant difference was demonstrated in the later gestation, group 2 (n = 8) fetal analyses; mean difference between consensus and actual gestation for normal fetuses was 0.9 weeks (SD of 1.5 weeks) versus -0.5 weeks (SD of 1.1 weeks) for the agenesis of corpus callosum cases (P = .046), suggestive of delayed sulcation in callosal agenesis. Delayed sulcation encountered in third trimester fetuses with agenesis of the corpus callosum may be seen and does not in itself imply an additional brain abnormality.

Agenesia del corpo calloso in feti con ventricolomegalia lieve: ruolo della RM

We evaluated the role of magnetic resonance (MR) imaging in the diagnosis of corpus callosum agenesis - isolated or associated with other anomalies - in fetuses with mild cerebral ventriculomegaly, as depicted at prenatal sonography. Between January 2005 and March 2007, 33 fetuses with a mean gestational age of 28.9 weeks (range 17-37) and mild ventriculomegaly diagnosed at prenatal sonography were included in this prospective study. All fetuses underwent MR imaging according to the following protocol: half-Fourier T2-weighted images along the three orthogonal plane according to the longitudinal axis of the mother, and subsequently three orthogonal planes were acquired according to the fetal brain. Quantitative image analysis included the size of the transverse diameter of the lateral ventricles, in the axial plane, and the thickness of the adjacent cerebral cortex. Qualitative image analysis included morphology of the lateral ventricles (normal, parallel pattern colpocephaly), signal intensity changes of the fetal brain, interruption of the germinative matrix, agenesis of the corpus callosum (complete/partial) and associated malformations. Postnatal physical examination and diagnostic imaging, as well as surgery, were the standard of diagnosis. Mean axial diameter of the lateral ventricle was 11.6 mm (range 10-15 mm), and mean thickness of the adjacent cerebral cortex was 2.1 mm (range 1.8-3 mm); 23/33 fetuses (70%) showed normal morphology of the lateral ventricles, and 8/33 (24%) showed abnormal morphology (parallel pattern, colpocephaly). The entire corpus callosum was visualised in 20/33 fetuses (60%). In 8/33 fetuses (25%), partial agenesis was diagnosed, whereas in 5/33 (15%), there was hypogenesis. In 6/13 fetuses (46%), isolated corpus callosum agenesis was detected, and two cases of hypogenesis of the corpus callosum were misinterpreted - overestimated in one case and underestimated in another. MR imaging may prove to be a useful second-line imaging modality in the prenatal diagnosis of corpus callosum agenesis in fetuses with mild ventriculomegaly.

Genetic malformations of cortical development

The malformations of the cerebral cortex represent a major cause of developmental disabilities, severe epilepsy and reproductive disadvantage. The advent of high-resolution MRI techniques has facilitated the in vivo identification of a large group of cortical malformation phenotypes. Several malformation syndromes caused by abnormal cortical development have been recognised and specific causative gene defects have been identified. Periventricular nodular heterotopia (PNH) is a malformation of neuronal migration in which a subset of neurons fails to migrate into the developing cerebral cortex. X-linked PNH is mainly seen in females and is often associated with focal epilepsy. FLNA mutations have been reported in all familial cases and in about 25% of sporadic patients. A rare recessive form of PNH due ARGEF2 gene mutations has also been reported in children with microcephaly, severe delay and early seizures. Lissencephaly-pachygyria and subcortical band heterotopia (SBH) are disorders of neuronal migration and represent a malformative spectrum resulting from mutations of either LIS1 or DCX genes. LIS1 mutations cause a more severe malformation in the posterior brain regions. Most children have severe developmental delay and infantile spasms, but milder phenotypes are on record, including posterior SBH owing to mosaic mutations of LIS1. DCX mutations usually cause anteriorly predominant lissencephaly in males and SBH in female patients. Mutations of DCX have also been found in male patients with anterior SBH and in female relatives with normal brain magnetic resonance imaging. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the reelin (RELN) gene. X-linked lissencephaly with corpus callosum agenesis and ambiguous genitalia in genotypic males is associated with mutations of the ARX gene. Affected boys have severe delay and seizures with suppression-burst EEG. Early death is frequent. Carrier female patients can have isolated corpus callosum agenesis. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to chromosome Xq28 in some pedigrees, autosomal dominant or recessive inheritance in others, and an association with chromosome 22q11.2 deletion in some patients. About 65% of patients have severe epilepsy. Recessive bilateral frontoparietal polymicrogyria has been associated with mutations of the GPR56 gene. Epilepsy is often present in patients with cortical malformations and tends to be severe, although its incidence and type vary in different malformations. It is estimated that up to 40% of children with drug-resistant epilepsy have a cortical malformation. However, the physiopathological mechanisms relating cortical malformations to epilepsy remain elusive.

Topical Review: Neuronal Migration Disorders, Genetics, and Epileptogenesis

Several malformation syndromes with abnormal cortical development have been recognized. Specific causative gene defects and characteristic electroclinical patterns have been identified for some. X-linked periventricular nodular heterotopia is mainly seen in female patients and is often associated with focal epilepsy. FLN1 mutations have been reported in all familial cases and in about 25% of sporadic patients. A rare recessive form of periventricular nodular heterotopia owing to ARGEF2 gene mutations has also been reported in children with microcephaly, severe delay, and early-onset seizures. Lissencephaly-pachygyria and subcortical band heterotopia represent a malformative spectrum resulting from mutations of either the LIS1 or the DCX (XLIS) gene. LIS1 mutations cause a more severe malformation posteriorly. Most children have severe developmental delay and infantile spasms, but milder phenotypes are on record, including posterior subcortical band heterotopia owing to mosaic mutations of LIS1. DCX mutations usually cause anteriorly predominant lissencephaly in male patients and subcortical band heterotopia in female patients. Mutations of the coding region of DCX were found in all reported pedigrees and in about 50% of sporadic female patients with subcortical band heterotopia. Mutations of XLIS have also been found in male patients with anterior subcortical band heterotopia and in female patients with normal brain magnetic resonance imaging. The thickness of the band and the severity of pachygyria correlate with the likelihood of developing severe epilepsy. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the reelin (RELN) gene. X-linked lissencephaly with corpus callosum agenesis and ambiguous genitalia in genotypic males is associated with mutations of the ARX gene. Affected boys have severe delay and infantile spasms with suppression-burst electroencephalograms. Early death is frequent. Carrier female patients can have isolated corpus callosum agenesis. Schizencephaly has a wide anatomoclinical spectrum, including focal epilepsy in most patients. Familial occurrence is rare. Initial reports of heterozygous mutations in the EMX2 gene have not been confirmed. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to chromosome Xq28 in some pedigrees, autosomal dominant or recessive inheritance in others, and an association with chromosome 22q11.2 deletion in some patients. About 65% of patients have severe epilepsy. Recessive bilateral frontoparietal polymicrogyria has been associated with mutations of the GPR56 gene.

Topical Review: Neuronal Migration Disorders, Genetics, and Epileptogenesis

Several malformation syndromes with abnormal cortical development have been recognized. Specific causative gene defects and characteristic electroclinical patterns have been identified for some. X-linked periventricular nodular heterotopia is mainly seen in female patients and is often associated with focal epilepsy. FLN1 mutations have been reported in all familial cases and in about 25% of sporadic patients. A rare recessive form of periventricular nodular heterotopia owing to ARGEF2 gene mutations has also been reported in children with microcephaly, severe delay, and early-onset seizures. Lissencephaly-pachygyria and subcortical band heterotopia represent a malformative spectrum resulting from mutations of either the LIS1 or the DCX ( XLIS) gene. LIS1 mutations cause a more severe malformation posteriorly. Most children have severe developmental delay and infantile spasms, but milder phenotypes are on record, including posterior subcortical band heterotopia owing to mosaic mutations of LIS1. DCX mutations usually cause anteriorly predominant lissencephaly in male patients and subcortical band heterotopia in female patients. Mutations of the coding region of DCX were found in all reported pedigrees and in about 50% of sporadic female patients with subcortical band heterotopia. Mutations of XLIS have also been found in male patients with anterior subcortical band heterotopia and in female patients with normal brain magnetic resonance imaging. The thickness of the band and the severity of pachygyria correlate with the likelihood of developing severe epilepsy. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the reelin ( RELN) gene. X-linked lissencephaly with corpus callosum agenesis and ambiguous genitalia in genotypic males is associated with mutations of the ARX gene. Affected boys have severe delay and infantile spasms with suppression-burst electroencephalograms. Early death is frequent. Carrier female patients can have isolated corpus callosum agenesis. Schizencephaly has a wide anatomoclinical spectrum, including focal epilepsy in most patients. Familial occurrence is rare. Initial reports of heterozygous mutations in the EMX2 gene have not been confirmed. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to chromosome Xq28 in some pedigrees, autosomal dominant or recessive inheritance in others, and an association with chromosome 22q11.2 deletion in some patients. About 65% of patients have severe epilepsy. Recessive bilateral frontoparietal polymicrogyria has been associated with mutations of the GPR56 gene. ( J Child Neurol 2005;20:287—299).

307 Prospective study of children with isolated corpus callosum agenesis prenatally diagnosed

307 Prospective study of children with isolated corpus callosum agenesis prenatally diagnosed