Disorder Of Cerebral Cortical Development Research Articles

Comprehensive genomic analysis of patients with disorders of cerebral cortical development.

Malformations of cortical development (MCDs) manifest with structural brain anomalies that lead to neurologic sequelae, including epilepsy, cerebral palsy, developmental delay, and intellectual disability. To investigate the underlying genetic architecture of patients with disorders of cerebral cortical development, a cohort of 54 patients demonstrating neuroradiologic signs of MCDs was investigated. Individual genomes were interrogated for single-nucleotide variants (SNV) and copy number variants (CNV) with whole-exome sequencing and chromosomal microarray studies. Variation affecting known MCDs-associated genes was found in 16/54 cases, including 11 patients with SNV, 2 patients with CNV, and 3 patients with both CNV and SNV, at distinct loci. Diagnostic pathogenic SNV and potentially damaging variants of unknown significance (VUS) were identified in two groups of seven individuals each. We demonstrated that de novo variants are important among patients with MCDs as they were identified in 10/16 individuals with a molecular diagnosis. Three patients showed changes in known MCDs genes and a clinical phenotype beyond the usual characteristics observed, i.e., phenotypic expansion, for a particular known disease gene clinical entity. We also discovered 2 likely candidate genes, CDH4, and ASTN1, with human and animal studies supporting their roles in brain development, and 5 potential candidate genes. Our findings emphasize genetic heterogeneity of MCDs disorders and postulate potential novel candidate genes involved in cerebral cortical development.

Psychosis and Schizencephaly – A case report and systematic review

Psychotic symptoms have been reported in association with a wide array of brain abnormalities. Few published reports have examined the association between schizencephaly and psychiatric illness. Originally defined by Wilmarth and later by Yakolev and Wadsworth – Schizencephaly is an uncommon congenital disorder of cerebral cortical development, defined as a grey matter-lined cleft extending from the pial surface to the ventricle. The nosology is based on neuroradiologic findings and confirmed by neuropathology when available. The Clinical presentation and neurodevelopmental outcomes of the disorder vary and are usually related to the extent/areas of the brain involved. In this article we review the medical literature around Schizencephaly paying particular attention to the pathophysiology, etiology and diagnosis of such patients. We then present a case of Schizencephaly and first episode psychosis in a 16-year-old adolescent who was admitted to our inpatient psychiatric service. Lastly, we present the findings of a systematic review from PubMed whereby we summarize 10 cases of Schizencephaly with associated psychiatric symptoms.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Schizencephaly and psychosis: A case report

IntroductionSchizencephaly is a rare malformation of the central nervous system, a congenital disorder of cerebral cortical development resulting in the formation of abnormal unilateral or bilateral clefts in the cerebral hemispheres that extends from the pial surface to the ventricle. It often manifests with partial seizures, mental retardation and hemiparesis.ObjectiveTo illustrate a rare case of association between psychosis and schizencephaly and the implication of this association for understanding the biology of the psychosis.MethodsA literature search was performed on PubMed database using the key words schizencephaly, psychosis, brain diseases and retrieved papers were selected according to their relevance. The patient clinical record was reviewed.ResultsThe authors report a case of a 59-year-old male admitted into a psychiatric hospital with insomnia, disorganized behavior probably secondary to auditory hallucinations and mystic delusions. He also reported epilepsy and strabismus in his right eye since his childhood and right facial paresis. A head CT scan revealed a left deep cortico-ventricular parieto-occipital communication corresponding to schizencephaly.ConclusionsConsidering the theory that schizophrenia is associated with abnormal brain development, this case report may provide an example of a neurodevelopment abnormality that manifests as psychosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Epilepsy secondary to schizencephaly: A comparative study

Schizencephaly is an uncommon structural disorder of cerebral cortical development. There are few comparative studies evaluating epilepsy in that condition. The aim of this study is to analyze which factors are associated with the development of epilepsy in patients with schizencephaly. The study is a longitudinal, observational and comparative retrospective study of 35 pediatric patients with schizencephaly. The patients were divided into two groups: a group of 10 children who developed epilepsy and another group of 25 who had no clinical epileptic manifestations. Both groups were followed up and the data collected to analyze potential risk factors included demographic and prenatal data (prenatal event, family history of epilepsy), radiological features (location of the cleft, unilateral or bilateral, extent of the lesion, number of impaired lobes, open-lip or closed-lip types, presence of associated anomalies), and neurological and electroencephalographic data. No significant difference was found in the association between epilepsy and any of the examined factors (<i>P</i> > 0.05). Neither the features of the lesion (cleft size location, type of lip, number of impaired lobes, associated anomalies), nor electroencephalography abnormalities, nor the family history of epilepsy or prenatal events could predict the occurrence of epilepsy in patients with schizencephaly.

English

Schizencephaly (spilt brain) is an uncommon disorder of cerebral cortical development, characterized by congenital clefts spanning the cerebral hemispheres from the pial surface to the lateral ventricles and lined by dysplastic cortical gray matter, the condition is present at birth and present early in life. Here we present an adult patient of open lip schizencephaly associated with absent septum pellucidum and arachnoid cyst presenting with seizure on and off for past four years.

A case of schizencephaly

Schizencephaly is a rare congenital disorder of cerebral cortical development. It is a neuronal migration anomaly, caused byinsults to migrating neuroblasts during 3rd to 5th gestational months. We encountered schizencephaly in the cranial magnetic resonance imaging (MRI) of a 4 month-old male baby. MRI demonstrated wide clefts occupying parietal regions bilaterally and the right occipital region partly. These areas were connected with lateral ventricles and also filled with cerebrospinal fluid. Although prevalence of this disorder is quite low and its incidence is unknown and also there may be no clearsymptoms as in our case, we emphasize that it should not be overlooked in differential diagnosis

P02 - 362 - Schizencephaly and psychosis

Schizencephaly is an uncommon congenital disorder of cerebral cortical development, defined as a gray matter-lined cleft extending from the pial surface to the ventricle. It is a neuronal migration anomaly, caused by insults to migrating neuroblasts during 3rd to 5th gestational months.Ischemia, germline mutations, intrauterine infections and exposure to drugs have been implicated in its etiology. The outcome relates with the severity of pathology. Unilateral closed lip schizencephaly has the mildest clinical picture and bilateral open lip the most severe. The most prominent manifestations are motor deficits and seizures.Schizencephaly has been related with psychosis. However, there is paucity of literature exploring this relation. Pubmed search with “Schizencephaly AND Psychotic disorders OR Bipolar Disorders” as Mesh terms resulted in 9 results. Of these four discussed Schizencephaly. Rest five reports were related to other disorders of cortical malformation. We present an interesting case of schizencephaly associated with psychosis and congenital hemiparesis. We also present a review of literature available for this rare association.This case points towards the role of neurodevelopmental abnormalities in the manifestation of psychosis and bipolar affective disorder. It indicates that presence of neurodevelopmental anomalies may have pathoplastic effects on the presentation of psychosis and may also influence treatment response adversely. A possible mechanism explaining the development of psychosis in schizencephaly is the disruption in intracortical connections. There is also a possibility of underlying ictal phenomenon leading to psychosis. The above case provides support to the neurodevelopmental theory of Schizophrenia.

No major role for the EMX2 gene in schizencephaly

Schizencephaly (SCH) is a rare disorder of cerebral cortical development, characterized by full thickness clefts spanning the wall of the cerebral hemispheres that are lined and surrounded by polymicrogyric cortex. Based on pathological analysis, SCH was originally considered to have multiple causes including infectious and vascular injuries, and toxic agents. However, a few reports of familial SCH have suggested a possible genetic etiology. Ten years ago two articles identified EMX2 as the first causative gene for human SCH in 13 of 18 patients, although for several putative mutations no pathogenic role was demonstrated. Here, we reinterpret the original articles as showing a significantly lower mutational rate (17%) than originally reported (72%), and provide results of EMX2 sequencing in 39 new SCH patients, detecting no pathogenic mutations. We conclude that the reported association between SCH and EMX2 mutations is not adequately supported by current data, and that diagnostic testing of EMX2 is not justified, as any results would be uninterpretable.

Schizencephaly: clinical and imaging features in 30 infantile cases.

Schizencephaly is an uncommon structural disorder of cerebral cortical development, characterized by congenital clefts spanning the cerebral hemispheres from the pial surface to the lateral ventricles and lined by cortical gray matter. Either an antenatal environmental incident or a genetic origin could be responsible for this lesion which occurs between the third and fourth month of gestation. We report the clinical and cranial imaging features of 30 children, of whom 15 had unilateral and 15 had bilateral lesions. Their ages at the time of the first presentation ranged from 1 month to 10 years. They were thoroughly studied from clinical, epileptical, imaging and electroencephalographic (EEG) viewpoints. Five patients were investigated by cranial computed tomography (CT), eight by cranial magnetic resonance (MR) imaging, and 17 by both methods. The clinical features consisted of mild hemiparesis in 17 cases (57%), 12/17 were related to a unilateral phenotype (80% of all unilateral forms) and 5/17 to a bilateral phenotype. A tetraparesis was present in nine cases, all of which were due to a bilateral cleft. Bilateral forms were significantly associated with tetraparesis, whereas unilateral forms were associated with hemiparesis. Mental retardation was observed in 17 cases (57%), and was observed significantly more often in bilateral clefts (80%). When both hemispheres are involved, an absence of reorganization of the brain function between the two hemispheres leads to severe mental deficits, in addition to the cerebral anomaly itself. Eleven patients had seizures (seven from unilateral and three from bilateral forms). The degree of malformation was not related to the severity of epilepsy. Migration disorders, such as dysplasia or heterotopia, were observed in 30% of cases and are also important etiopathogenetic factors. The septum pellucidum was absent in 13 cases (43%), with septo-optical dysplasia in two cases. Corpus callosum dysgenesis was noted in 30% of cases. Four cases of mega cisterna magna were noted. Although familial cases and environmental factors have been previously reported, schizencephaly appears to be, in the majority of cases, sporadic.

Schizencephaly

Schizencephaly is an uncommon congenital disorder of cerebral cortical development. Although a well-recognized cause of seizures and developmental deficits in children, previous reports describe the range of neurodevelopmental outcome in only 47 patients. We report the clinical and cranial imaging features of 47 children with unilateral open-lip (17), unilateral closed-lip (12), bilateral open-lip (12), and bilateral closed-lip (6) schizencephaly, as defined radiologically. The schizencephalic cleft occurred more often in the anterior than in the posterior neocortex. Children with closed-lip schizencephaly presented with hemiparesis or motor delay whereas patients with open-lip schizencephaly presented with hydrocephalus or seizures. Forty-three patients (91%) had associated cerebral developmental anomalies, most commonly absence of the septum pellucidum (45%) and focal cortical dysplasia (40%). There was a history of seizures in 57% of cases, a third of which were classified as difficult to control. Neurodevelopmental outcome was generally poor, with 51% of patients (24/47) having severe deficits, 32% of patients (15/47) having moderate impairment, and 17% of patients (8/47) having mild or no problems. Patients with closed-lip schizencephaly were more likely to have a mild to moderate outcome than those with open-lip type (78% versus 31%; p < 0.05). Children with unilateral schizencephaly had a mild or moderate outcome more frequently than those with bilateral lesions (62% versus 28%; p < 0.05). Children who had involvement of a single lobe accounted for 88% of those with mild outcomes and 53% of those with moderate outcomes. Unilateral closed-lip schizencephaly was associated with the best neurodevelopmental outcome; in contrast, 11 of 12 children with bilateral open-lip clefts had severe disabilities. Language development was significantly more likely to be normal in those children with unilateral schizencephaly than in those with bilateral clefts (48% versus 6%; p < 0.002). Thus, the presentation and outcome of children with schizencephaly are quite variable but are related to the extent of cortex involved in the schizencephalic defect.