Schizencephaly …

Harvey B Sarnat MS MD FRCPC

Developmental Malformations

Updated 10.13.2024
Released 07.28.1994
Expires For CME 10.13.2027

Schizencephaly

Author: Harvey B Sarnat MS MD FRCPC

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Schizencephaly

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Introduction

Overview

Schizencephalies are fetal brain disruptions characterized by cerebral clefts lined by dysplastic polymicrogyric cortex extending medially from the pial surface to the lateral ventricles. Schizencephaly is the result of a disruption of cerebral development, most probably arising during the early second trimester of pregnancy. The severity of the clinical picture, made up of motor deficits, intellectual disability, and epilepsy, is related to type, location, and size of the clefts and the presence of associated brain abnormalities and identified genetic defects. Schizencephaly may be unilateral or bilateral and is not limited by gender or ethnicity.

Key points

	• Polymicrogyria, ie, patches of minute gyri are present in open and closed lip schizencephaly, borders the defect. These mini-gyri have pial discontinuities that enable synaptic short-circuiting between adjacent gyri and increase the risk of epilepsy.
	• Schizencephaly associated with porencephaly is secondary to genetic or environmental causes that interfere with circulation, resulting in infarction, usually in the middle cerebral arterial territory, but also from venous obstructions.
	• Careful history taking may reveal acquired epigenetic damage in utero (eg, by use of cocaine and other teratogens).
	• Molecular genetic studies may reveal defects commonly associated with hemorrhagic or thrombotic disease, mimicking acquired lesions. The most frequent is COL4A1 mutation.
	• Clinical manifestations include motor deficits (eg, spastic hemiparesis or diparesis), language, intellectual deficits, psychiatric disorders, and epilepsy.
	• The onset of epilepsy is usually in infancy or early childhood but may be delayed even to adult life.

Historical note and terminology

Schizencephalies are congenital clefts that unilaterally or bilaterally extend from the pial surface of the lateral parts of the cerebral cortex to the lateral ventricle. The opposing borders of each separate cleft are covered by abnormal neocortex, structured as polymicrogyria, a developmental anomaly. The presence of polymicrogyria is consistent with an origin during the migratory or early postmigratory period of neocortical development, including lamination of the cortical plate to produce mature cortical organization.

Schizencephaly was first described by Wilmarth in 1887 (111). The term is derived from the Greek word “schizen,” which means to divide and was introduced by Yakovlev and Wadsworth in 1946. Two types of schizencephaly are defined by these authors: the closed lips and the open lips types (116; 117). In the closed-lips type, the defects that connect the arachnoid and ventricular spaces are lined by pial-ependymal seams. The seams merge tightly like a zipper, isolating the arachnoid space from the lateral ventricle. The dysplastic neocortex beneath the seam manifests polymicrogyria, an anomaly of cortical development that is detectable on MRI, adding evidence of the fetal origin of the lesion. The open-lips type of schizencephaly presents as an open connection between arachnoid and ventricular spaces. Viewed from outside the brain, the opercula are malformed and not fully approximated (96). Some authors attempt to classify schizencephalies by morphology criteria and other associated brain anomalies, such as the state of the septum pellucidum (43).

Porencephaly, an inborn unilateral or bilateral cerebral mantle defect, shares some properties with schizencephaly but differs from the latter by the absence of ectopic abnormal grey matter lining the defect. It arises as a later disruption of cerebral development after cortical development has reached a mature stage, with migration of cortical neurons completed. Insights in the morphogenesis of both disorders has deepened in the last decades due to refined imaging techniques and discoveries in the field of genetics. Breedveld and colleagues showed mutations of COL4A1, associated with porencephaly (15). COL4A1 encodes a vascular basement protein known from previous studies to be involved in cases of cerebral hemorrhage and thrombosis. Yoneda and colleagues showed pathogenic mutations of COL4A1 to be linked to schizencephaly (118). The convergent findings support a link between cases of porencephaly and schizencephaly. From these and later studies, it transpires that the morphological difference between schizencephaly and porencephaly depends on the stage of neocortical development at the time of the insult: schizencephaly resulting from a lesion during corticogenesis, whereas porencephaly has its time of origin after a stable ordering of cortical layers is reached. These and other studies point to a vascular/ischemic mechanism underlying schizencephaly. Not all cases are related to genetic defects. Exogenous causes cannot be dismissed. Indeed, epidemiologic findings indicate that exogenous causes interfering with pregnancy have to be considered in addition to genetic defects. Exogenous causes also include cytomegalovirus and possibly toxic agents in early pregnancy, including the use of cocaine (53).

Schizencephalies originate in the middle fetal period when neocortical neurons have not yet established their definite place in vertical and horizontal organization, and movement of the neuronal somata is still possible. Disruptions affecting the evolution of the neocortex during this period may result in disordered vertical and horizontal register of the cortical layers, presenting as polymicrogyria. Polymicrogyria arises during the neuronal migration period, extending to the stabilization period during which connectivity within and to the outside connections of the neocortex is achieved. Polymicrogyria presents on MRI as very small fused gyri.

Porencephalies are generally thought to arise from a destructive process. Porencephaly and schizencephaly share morphological features, but the term schizencephaly, first coined by Yakovlev and Wadsworth, is reserved for cases in which polymicrogyric cortical tissue overlies the defects (116; 117). These authors emphasized the malformative nature and early ontogenetic origin of schizencephalies. They also distinguished type 1 (or closed-lip) schizencephaly, in which the walls of the cleft are in contact with each other, and type 2 (or open-lip) schizencephaly, characterized by separated lips and cerebrospinal fluid-filled clefts. Although type 1 is well-defined, type 2 is much more diverse in shape, extent, and associated abnormal findings. In some patients, bilateral schizencephaly may be closed on one side and open on the other side.

Coronal section of cerebrum of adult with schizencephaly

On the left side tiny microgyri connect the ventricle to the normal cortex (asterisk). On the right side the schizencephaly has separated lips, causing an open connection between the lateral ventricle and the convexity of the brai...
Scheme of normal and polymicrogyric cortex

On the right side a schematic representation of 4-layered polymicrogyric cortex. Note that the undulating surface of layer 2 is not wound around visible sulci as in the normal cortex, lending the surface a smooth or crenated aspec...

Schizencephaly has been increasingly recognized in vivo due to the progressive refinement of neuroimaging techniques (08; 50; 06; 07). Although first-generation MR scanners did not achieve sufficient resolution to differentiate polymicrogyria from pachygyria, improvements have made this possible and, indeed, imperative for a definite diagnosis.

Sometimes full-thickness defects without polymicrogyria border the defect but with associated cortical malformation distant from the defect are classified as schizencephaly (62). In this way, the definition, especially of type 2, sometimes tends to become overstretched.

Genetic studies initially focused on EMX2, a homeobox gene, which could not be confirmed (28). Genetic, neuroradiological, and experimental studies have given ground to the vascular origin (fetal cerebral artery occlusion) as the most common etiology (59). The most frequent genetic mutation, usually de novo, associated with schizencephaly, particularly with arterial occlusive or hemorrhagic infarcts, is of the COL4A1 gene (77; 100; 01; 19; 59; 98). Because this mutation primarily involves endothelium of blood vessels, not only is the nervous system a target, but multiple organs might be affected and develop malformations. Vascular anomalies of the brain coexist in some cases (64). Congenital cataracts are seen in some patients. Arachnoidal cysts in the leptomeninges of the interhemispheric fissure or middle fossa may occur (02).

Clinical manifestations

Presentation and course

In nearly all patients affected by schizencephaly, the main clinical manifestations are motor deficits (usually spastic hemiparesis or diparesis), intellectual and cognitive deficits, mental retardation of various degrees, and epileptic seizures (13). Epilepsy usually occurs in infancy or childhood, but occasionally, an onset of seizures does not occur until adult life (58; 67). Some patients are not epileptic, however, or may show only subclinical paroxysmal activity on the EEG. Organization of the motor cortex may be disrupted and can be shown by transcranial magnetic stimulation and diffusion tensor imaging (05). Hemiparkinsonism was reported in one patient (99). Schizophrenia or psychosis is rare but is reported (109). Bipolar affective disorder also is described in some patients (91). However, the clinical outcome may be markedly different in different patients, and it is related to type, location, and size of the clefts as well as the presence of associated brain malformations (08; 38; 41; 86; 25; 74; 47).

Schizencephalies may be unilateral or bilateral and closed-lipped or open-lipped, and they may present as isolated malformations or be associated with other structural brain abnormalities such as agenesis of the corpus callosum and septum pellucidum, which may even be neurologically asymptomatic in some patients (35; 03). Rare cases of schizencephaly are associated with frontoethmoidal or occipital encephalocele (106; 54). Schizencephaly may be one-sided with a normal opposite hemisphere or with focal contralateral polymicrogyria without cleft. Schizencephaly may also be part of more complex malformations (in the case of septo-optic dysplasia, for example) (81; 12). They may be isolated or associated with other supratentorial (polymicrogyria, agenesis of corpus callosum and septum pellucidum) or infratentorial brain abnormalities, such as cerebellar clefts (90) or also may present as part of more complex malformations, such as septo-optic dysplasia (SOD) (81; 76; 13).

Left prerolandic schizencephaly (MRI)

The cleft is lined by polymicrogyric cortex. (Contributed by Dr. Giorgio Battaglia.)

Obviously, patients with large bilateral open-lip clefts or septo-optic dysplasia are characterized by the more severe clinical pictures, whereas those with small, unilateral closed-lip clefts display the mildest clinical signs (22; 76; 58).

Several cases have been reported with syndromic associations (eg, LEOPARD syndrome) (72), Prune belly syndrome, and Nijmegen breakage syndrome (104). A note of caution should be added in cases where hydrocephalus coexists with open lips connecting the arachnoid space and the lateral ventricle. Infolding of the cortex towards the ventricle may falsely suggest an appearance of a seam lined by abnormal cortex, especially when the resolution of the images is less than optimal to detect polymicrogyria.

Patients with bilateral schizencephaly, particularly if open-lipped, may present with unilateral or bilateral congenital hemiparesis, severe hypotonia, and developmental delay (25; 115) or develop spastic diparesis, often associated with microcephalia and other neurologic deficits such as apraxia and pseudobulbar paralysis. Mental retardation and delay in language development are associated findings, particularly when more cerebral lobes are involved (86). In addition, progressive obstructive hydrocephalus may develop during the first months of life (86).

In patients with unilateral clefts, motor deficits are frequently present on the side contralateral to the cleft. They range in severity from mild asymmetry of motor skills to spastic hemiparesis (79). Bilateral motor deficits have been reported in few patients, likely related to the presence of cortical dysgeneses contralateral to the cleft. The mental abilities are usually normal in patients with unilateral closed or small open cleft, whereas mental retardation is common in patients with larger clefts (49). Delay in language development and dissociative language representation in the cortex are also related to the presence of open clefts, fronto-parietal location, and extent of the malformation, rather than to the side of the schizencephaly (86; 25; 66).

Analysis of cortical functions has been reported in a few patients with unilateral schizencephaly. Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation have demonstrated that the unaffected motor cortex innervates both hand muscles, thus, indicating functional reorganization of the motor areas in patients with schizencephaly (70; 110; 61; 05). In an asymptomatic patient with left frontal schizencephaly, fMRI revealed activation of the dysgenetic cortex lining the cleft, suggesting a contribution of the malformed cortex in physiologic cerebral functions (101). Another fMRI study in an adult with one-sided full thickness schizencephaly and adult-onset dystonia in the affected half of the body showed activation in the abnormal cortex surrounding the cleft on attempted movement of the contralateral limbs (113). The authors also suggested a role for neuromodulation by transcranial magnetic stimulation to suppress abnormal activity of the area surrounding the cleft.

Focal epilepsy is a frequent finding in both unilateral and bilateral cases. It is present in about half of the cases, and it is refractory to antiepileptic drugs in about a third (38; 63). Bilateral schizencephaly has a higher risk of seizures than unilateral forms (63). In all patients, seizures are mostly focal, and their semeiology is related to the cleft location (39; 17). Focal temporal lobe seizures were precipitated by intermittent photic stimulation during an EEG recording in a 12-year-old boy with schizencephaly and pachygyria (14).

Though onset of epilepsy is usually in infancy or early childhood, rarely some patients may not develop seizures until adult life (10; 58; 67). Schizencephaly was first discovered during the evaluation of seizures during labor in a woman in her late 30s (88). Psychiatric presentations, including psychosis, can disclose schizencephaly on brain imaging, as in the case of a 50-year-old man (87).

Seizures are usually focal motor, but other types can occur as well. Infantile spasms, myoclonic seizures, or atonic seizures are rarely reported. The presence and severity of epilepsy is not necessarily related to the severity of the anatomical malformation (39; 25). Seizures may be the presenting symptom in patients with unilateral cleft with mild or no neurologic deficits (39; 22). Even in patients with refractory seizures, epilepsy is not usually characterized by a malignant course, affecting the neurodevelopmental outcome (39; 86; 25). A rare form of seizures, focal hypsarrhythmia with clusters of epileptic spasms, was seen in a group of 12 patients, including 11 with severe focal developmental lesions, of which two had open lip schizencephaly (18). Surgery should be seriously considered in this group.

Prognosis and complications

The prognosis depends on the size and extent of schizencephaly and the presence and location of associated cerebral dysgeneses. In the case of a pathogenic COL4A1 mutation, vascular complications in later life may occur. Clinical manifestations include seizures, cerebral palsy, and intellectual impairment. Patients with bilateral cleft and associated complex brain malformations can be severely handicapped in everyday life. Progressive obstructive hydrocephalus in open-lip schizencephaly may require a ventriculoperitoneal shunt (86). Epilepsy, when present, is characterized by focal seizures of multiple types, which can sometimes be difficult to control (41). By contrast, patients with a single fused cleft have minor motor deficits and normal mental abilities and can lead a normal social life. Epilepsy is often the main clinical problem because focal seizures are resistant to treatment in about one third of the cases (08; 38; 41). A lesion on one side may be functionally compensated by ipsilateral innervation from the unaffected cortex in unilateral schizencephaly (20; 113).

When schizencephaly is caused by COL4A1 mutation, siblings and one of the parents may be affected as well, and medical supervision is advised to cope with the risk of later vascular problems.

Clinical vignette

Case 1. The patient, now 30 years old, was born at term after an uneventful pregnancy and delivery. Motor and mental development were both normal. The clinical history was uneventful until age 22 years when a generalized tonic-clonic seizure occurred during sleep. EEG recordings demonstrated diffuse epileptic abnormalities. The patient was given phenobarbital 50 mg daily for 6 years and had no seizure recurrence. Six months after treatment withdrawal, two convulsive seizures occurred during sleep, preceded by oral automatisms in one case. The treatment with phenobarbital was again started with complete seizure control. A small unilateral open lip schizencephaly in the left temporoparietal region was revealed by MRI.

Left unilateral open-lip cleft in the parietotemporal region (MRI)

The cleft is lined by polymicrogyric cortex; the left lateral ventricle is enlarged and shows a dimple where it communicates with the cleft. (Contributed by Dr. Geoffrey Miller.)

Case 2. The patient, now 8 years old, was adopted at age 2 days. No information on family history or pregnancy was available. The infant was born at term by spontaneous delivery; the weight at birth was 3710 g, and the neonatal general conditions were reported to be good. The early stages of motor development were slightly delayed, and the child was unable to use his right hand. Neurologic examination at age 14 months was characterized by asymmetric spastic diplegia, which was more severe on the right side and also involved the right upper limb. Bilateral schizencephaly (open-lipped on the left and closed-lipped on the right side) associated with an absence of septum pellucidum and bilateral thickening of the frontal cortex was demonstrated by MRI.

Bilateral frontal schizencephaly (MRI)

The coronal image shows open-lip left schizencephaly, closed-lip right schizencephaly, the absence of septum pellucidum, and thickened frontal cortex. (Contributed by Dr. Giorgio Battaglia.)

A single convulsive seizure occurred during hyperthermia at age 22 months; no treatment was given, and no further seizures occurred despite the presence of high incidence EEG interictal epileptic abnormalities.

Interictal epileptic abnormalities in bilateral frontal schizencephaly (EEG)

Diffuse discharges of irregular sharp and slow wave complexes are more evident on the anterior leads. The interictal activity is often of larger amplitude on the left side (boxed area). (Contributed by Dr. Giorgio Battaglia.)

Kinesitherapy produced a positive effect on motor skills; the boy is now able to reach the standing position and walk with assistance. The general intelligence quotient, assessed by the Griffith Scale (with exclusion of locomotor scale) at age 8.4 years, was 76, equivalent to that of a 6.4-year-old child.

Case 3. This boy presented with left arm paresis at the age of 4 months. The pregnancy was complicated by attempted abortion with an unidentified drug in the third month of gestation. When presenting to the pediatric neurologist at 11 years of age, he had spastic monoparesis of the left arm. Otherwise, his behavior and motor performance were normal. On psychological testing he had low normal intelligence. He had no clinical signs of epilepsy. MR of the head showed right-sided neocortical dysplasia with polymicrogyria involving the central motor region and large adjacent area of the frontal lobe. Schizencephaly appeared open on the outside but closed near the ventricle.

11-year-old boy with left-sided schizencephaly bordered by dysplastic cortex (MRI)

The lesion appears open at the outside, but is closed where it reaches the ependyma. (Contributed by Peter G Barth MD.)
11-year-old boy with left-sided schizencephaly (MRI)

Section above the defect shows widespread polymicrogyria. Note the perpendicular strokes of gray cortical matter without intervening sulci. (Contributed by Peter G Barth MD.)
11-year-old boy with left-sided schizencephaly (sagittal MRI)

This section localizes the defect in the central motor zone with additional patches of polymicrogyria advancing in the premotor left frontal lobe region. (Contributed by Peter G Barth MD.)

Biological basis

Etiology and pathogenesis

Schizencephaly is a transmantle defect of one or both cerebral hemispheres, lined by dysplastic polymicrogyric cortex. Some earlier theories held that schizencephaly is secondary to hypoperfusion or ischemic cortical injury; however, other gestational causes such as infections, toxic agents, or trauma have been considered as possible relevant causes (24; 09; 27; 08; 53; 45).

A vascular etiology for schizencephaly and porencephaly has been established, linking both disorders. An ipsilateral absence of the middle cerebral artery has been observed in two of three cases of schizencephaly studied by MRI and magnetic resonance angiography (29). Gould and colleagues discovered a mutation in the Col4A1 gene in a mouse mutant with perinatal hemorrhage and porencephaly (36). The same mutation also occurs in humans with brain anomalies that can include schizencephaly (77; 100; 01; 19; 59; 98; 33). Electron microscopic study showed an abnormal structure of the vascular basement membrane, explaining the tendency to hemorrhage or thrombosis. Human cases of COL4A1 mutations also are associated with schizencephaly (19; 98; 112; 114). Pathogenic monoallelic mutations of the human homologue COL4A1 were subsequently found in several families with recurrent porencephaly by the same group. COL4A1 mutations were also found to underlie cases of familial schizencephaly and porencephaly in a larger study by Yoneda and colleagues (118). Of 61 patients with porencephaly, 15 were found to carry a monoallelic mutation in COL4A1. Of 10 patients with schizencephaly, five carried a mutation. Both de novo and familial cases were identified. Variable findings included hemolytic anemia, optic atrophy, and elevated creatine kinase. Chromosomopathies are not usually described in schizencephaly, but deletion of 22q13.32 was reported in one case who also had an occipital encephalocele (54), and an 8p23.1 microdeletion in a fetus with partial callosal agenesis and schizencephaly was reported (21). Mutations in α- and β-tubulin encoding genes, tubulin being a microtubule-associated protein, involve differentiating neuroblasts even when first expressing neuronal cellular lineage and can generate a spectrum of brain malformations, including agenesis of the forebrain commissures and schizencephaly (93). Contactin-associated protein with two genetic mutations is reported in one patient with bilateral schizencephaly (94).

Porencephaly resembling or associated with schizencephaly is usually due to middle cerebral arterial occlusion during the second trimester of fetal life, but venous anomalies related to a poorly formed great vein of Galen, persistent falcine sinus, and cerebral venous thrombosis also are reported (114; 103).

A large epidemiologic study by Curry and colleagues in California involved more than 4 million births from 1985 to 2001, giving a population prevalence of 1.54/100,000 (23). Young parental age and monozygotic twinning were risk factors. Associated anomalies pointing to vascular disruption were found, including gastroschisis, bowel atresias, and amniotic band disruption. A possible role in the prenatal use of cocaine or other street drugs is documented by the study of Dominguez and colleagues (27).

Heterozygous mutations of the homeobox gene EMX2 have been reported in a few schizencephaly patients (16; 28; 40). However, EMX2 screening of larger cohorts of patients affected by schizencephaly revealed no pathologic EMX2 mutations (41; 107; 80).

Septo-optic dysplasia (de Morsier syndrome, SOD, OMIM 182230) is a heterogenous congenital malformation complex. Its diagnosis requires the combined presence of two of three congenital defects: (1) optic nerve hypoplasia, (2) pituitary hypofunction, and (3) midline brain abnormalities, typically dysgenesis of the septum pellucidum or corpus callosum (04; 13; 35). In a series of 17 patients with septo-optic dysplasia evaluated by MRI, only three had schizencephaly (04). Nevertheless, septo-optic-pituitary dysplasia remains one of the strongest associated malformations with schizencephaly and may also involve hypoplasia of the olfactory bulbs and tracts (97; 13; 11; 75; 58). Septo-optic dysplasia with schizencephaly has been called “septo-optic dysplasia plus syndrome” (46). For more information, see the article “Septo-optic-pituitary dysplasia” in Medlink Neurology. HESX1 and SOX2 genes, previously associated with septo-optic dysplasia, were tested in a large cohort of 75 schizencephaly patients, including open and closed types, with negative results (78). No pathogenic mutations were found. Two unrelated cases of schizencephaly in young female infants were associated with thrombophilia caused by mutations in the genes for methyltetrahydrofolate reductase and factor V Leiden (42). Hereditary hemorrhagic telangiectasia with schizencephaly has been reported (32).

Schizencephaly is determined by impairment during brain ontogenesis of the mechanisms that govern neuroblast migration and cortical organization. Ischemic cortical injuries and infective agents have been considered causative factors. Polymicrogyria is present in about half of the affected patients within or adjacent to the schizencephalic clefts (50). This finding supports the hypothesis that both polymicrogyria and schizencephaly may be caused by cortical ischemic damage (09; 08). Polymicrogyria consists of small irregular gyri without sulci or with sulci bridged by fusion of the overlying molecular layer (31). It is sometimes believed to arise from cortical ischemic necrosis primarily affecting the fifth cortical layer (95). Two types of polymicrogyria have been described: (1) the 4-layered type, possibly due to a late second-trimester insult (92), and (2) the unlayered type, possibly due to an early second-trimester insult (30). Normal cortical lamination may also be seen in some microgyri (102; 55). One of the most important neuropathological features of polymicrogyria not appreciated at the macroscopic resolution of MRI is that the lateral walls of adjacent microgyri often exhibit gaps or discontinuities in the pia mater that result in fusion of their molecular zones (102; 55). This abnormal fusion between gyri may enable synaptic “short-circuiting” that could become epileptogenic.

Mild ischemic damage could determine polymicrogyria without cortical infolding, whereas severe and earlier damage deeply involving radial glial fibers could determine a full-thickness cortical cleft lined by unlayered polymicrogyria (08). In addition, transmissible agents may produce schizencephaly, as indicated by the presence of cytomegalovirus DNA and antibodies in two affected children (53). Indeed, full-thickness cerebral clefts can be experimentally induced in hamsters by intraplacental inoculation of Kilham strain of mumps virus (105).

Few classical studies are available regarding the neuropathology of schizencephaly (24). The clefts are more frequently located around the Sylvian fissures, but they can also involve the prefrontal and, more rarely, the temporal and occipital lobes. In severe bilateral cases, the descending cortical projections are virtually absent, whereas the striatum is hyperplastic (117). The polymicrogyric cortex surrounding the clefts shows no recognizable layering (68).

In a remarkable study, prenatally diagnosed cases by fetal MRI were compared to MR findings at postnatal follow-up (83). Some cases shown to have open lip type schizencephaly had a closed-lip appearance of their brains on follow-up. The finding adds to the possibility of a fetal disruption in more cases, whether caused by accident or genetic mutation. In another study where the development of the clefts was monitored, the approximation of the clefts and the apparent closure like a zipper was confirmed on intrauterine and postnatal and postnatal follow-ups (65). Mechanical factors of incomplete or imperfect closure of the telencephalic flexure may play an important role even in cases of genetically determined etiology (96). This neurodevelopmental dysplasia can be detected and quantitated in the fetus by ultrasonography or fetal MRI (89).

Schizencephaly in the region of the Sylvian fissure is almost universally associated with polymicrogyria in its walls.

Diagnostic workup

Diagnosis rests on neuroimaging. A careful neuroradiologic evaluation of the type and extent of the clefts and of associated brain malformations is crucial to the patient assessment, given the correlation between anatomic features and clinical outcome. MRI is the best choice to reveal the cortical cleft lined by gray matter, the cleft extension to the lateral ventricle, and the resultant dimpling of the ventricular walls. Fetal MRI may provide a prenatal diagnosis and disclose associated intracranial anomalies (34).

Left unilateral open-lip cleft in the parietotemporal region (MRI)

The cleft is lined by polymicrogyric cortex; the left lateral ventricle is enlarged and shows a dimple where it communicates with the cleft. (Contributed by Dr. Geoffrey Miller.)

MRI also detects the associated malformations, such as agenesis of septum pellucidum and corpus callosum, areas of polymicrogyria adjacent to the cleft or symmetrically located in the contralateral hemisphere (08).

Corpus callosum agenesis (MRI)

Sagittal MRI shows partial agenesis of corpus callosum in a patient with bilateral schizencephaly. (Contributed by Dr. Geoffrey Miller.)

Single photon emission computed tomography and positron emission tomography revealed metabolic activity and perfusion in the walls of the cleft identical to that of normal cerebral cortex (82). Functional MRI studies reported sensorimotor and speech-related activation of the dysgenetic cortex lining the cleft, suggesting a contribution of the malformed cortex in physiologic cerebral functions (101; 56), but the functional relevance of such activation is still debated (110). Diffusion tensor imaging may reveal abnormalities of major fiber tracts in affected patients (61).

CT scan may reveal the gray matter lined cleft. In infants, the malformation should be suspected if CT or ultrasonography reveals corpus callosum agenesis and focal dilatation of the lateral ventricles. Prenatal ultrasonographic diagnosis may be possible in cases with large open clefts or associated with septo-optic dysplasia (85; 52; 89). Prenatal MRI may also differentiate developmental anomalies from destructive lesions (26; 85).

EEG is important because of the high risk of seizures in schizencephaly, and this noninvasive test may reveal potentially epileptogenic foci that are subclinical at the time of the recording. Stereo-EEG recording can localize the epileptogenic focus in schizencephaly better than routine recordings and provide an intraoperative guide for radiofrequency thermoablation (73).

In the case of schizencephaly, both parents and proband should be genetically screened with COL4A1 mutations in particular to be excluded. The diagnosis may sometimes be made prenatally by fetal MRI or ultrasonography (77; 59; 98).

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References

01: Abe Y, Matsuduka A, Okanari K, et al. A severe pulmonary complication in a patient with COL4A1-related disorder: a case rep. Eur J Med Genet 2017;60(3):169-71. PMID 28017902
02: Ahmed AK, Cohen AR. Intracranial arachnoid cysts. Childs Nerv Syst 2023;39(10):2771-8. PMID 37466684
03: Alkareem M, Ahmed H, Ahmed G. Unilateral right closed-lip schizencephaly. BMJ Case Rep 2020;13(9);e235004. PMID 32928828
04: Alt C, Shevell MI, Poulin C, Rosenblatt B, Saint-Martin C, Srour M. Clinical and radiologic xpectrum of septo-optic dysplasia: review of 17 cases. J Child Neurol 2017;32(9):797-803.** PMID 28482731
05: Baik SW, Kim GW, Ko MH, Seo JW, Won YH, Park SH. An unusual, intermediate-sized lesion affecting motor organization in a patient with schizencephaly: a case report. Front Hum Neurosci 2020;14:258. PMID 32765236
06: Barkovich AJ. Schizencephaly. Pediatric neuroimaging, 4th edition. Philadelphia: Lippincott Williams & Wilkins, 2005:334-7.
07: Barkovich AJ, Guerrini R, Kuzniecky RI, Jackson GD, Dobyns WB. A developmental and genetic classification for malformations of cortical development: update 2012. Brain 2012;135(Pt 5):1348-69. PMID 22427329
08: Barkovich AJ, Kjos BO. Schizencephaly: correlation of clinical findings with MR characteristics. Am J Neuroradiol 1992;13:85-94. PMID 1595498
09: Barth PG. Disorders of neuronal migration. Can J Neurol Sci 1987;14:1-16. PMID 3545413
10: Battah A, DaCosta TR, Shanker F, et al. Schizencephaly as an unusual cause of adult-onset epilepsy: a case report. Cureur 2022;14(6):e25848. PMID 35836438
11: Benson JC, Nascene D, Truwit C, McKinney AM. Septo-optic dysplasia: assessment of associated with special attention to the olfactory sulci and tracts. Clin Neuroradiol 2019;29(3):505-13. PMID 29663010
12: Bhatnagar S, Kuber R, Shah D, Kulkarni V. Unilateral closed lip schizencephaly with septo-optic dysplasia. Ann Med Health Sci Res 2014;4(2): 283-5. PMID 24761255
13: Braga VL, DaCosta MDS, Riera R, et al. Schizencephaly: a review of 734 patients. Pediatr Neurol 2018;87:23-9. PMID 30501885
14: Bratt NJ, Hampton CW. Intermittent photic stimulation triggers a temporal lobe seizure in a patient with schizencephaly and pachygyria. Epilepsy Behav Rep 2020;15:100395. PMID 33458644
15: Breedveld G, de Coo IF, Lequin MH, et al. Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. J Med Genet 2006;43(6):490-5. PMID 16107487
16: Brunelli S, Faiella A, Capra V, et al. Germline mutations in the homeobox gene EMX2 in patients with severe schizencephaly. Nature Genet 1996;12(1):94-6. PMID 8528262
17: Caraballo RH, Cersosimo RO, Fejerman N. Unilateral closed-lip schizencephaly and epilepsy: a comparison with cases of unilateral polymicrogyria. Brain Dev 2004;26(3):151-7. PMID 15030902
18: Caraballo RH, Reyes G, Falsaperla R, et al. Epileptic spasms in clusters with focal EEG paroxysms: A study of 12 patients. Seizure 2016;35:88-92. PMID 26803282
19: Cavallin M, Mine M, Philbert M, et al. Further refinement of COL4A1 and COL4A2 related cortical malformations. Eur J Med Genet 2018;61(12):765-72. PMID 30315939
20: Chang WH, Kim YB, Ohn SH, Park CH, Kim ST, Kim YH. Double decussated ipsilateral corticospinal tract in schizencephaly. Neuroreport 2009;20(16):1434-8. PMID 19770689
21: Chen CP, Peng CR, Chang TY, et al. Prenatal diagnosis of chromosome 8p23.31 microdeletion by array comparative genomic hybridization using uncultured amniocytes in a pregnancy associated with fetal partial corpus callosum agenesis and schizencephaly. Taiwan J Obstet Gynecol 2015;54(6):797-8. PMID 26701010
22: Cho WH, Seidenwurm D, Barkovich AJ. Adult-onset neurologic dysfunction associated with cortical malformations. Am J Neuroradiol 1999;20:1037-43. PMID 10445440
23: Curry CJ, Lammer EJ, Nelson V, Shaw GM. Schizencephaly: heterogeneous etiologies in a population of 4 million California births. Am J Med Genet 2005;137(2):181-9. PMID 16059942
24: Dekaban A. Large defects in cerebral hemispheres associated with cortical dysgenesis. J Neuropathol Exp Neurol 1965;24:512-38.
25: Denis D, Chateil JF, Brun M, et al. Schizencephaly: clinical and imaging features in 30 infantile cases. Brain Dev 2000;22(8):475-83. PMID 11111060
26: Denis D, Maugey-Laulom B, Carles D, Pedespan JM, Brun M, Chateil JF. Prenatal diagnosis of schizencephaly by fetal magnetic resonance imaging. Fetal Diagn Ther 2001;16(6):354-9. PMID 11694738
27: Dominguez R, Aguirre Vila-Coro A, Slopis JM, Bohan TP. Brain and ocular abnormalities in infants with in utero exposure to cocaine and other street drugs. Am J Dis Child 1991;145:688-95. PMID 1709777
28: Faiella A, Brunelli S, Granata T, et al. A number of schizencephaly patients including two brothers are heterozygous for germline mutations in the homeobox gene EMX2. Eur J Hum Genet 1997;5(4):186-90. PMID 9359037
29: Fernandez-Bouzas A, Harmony T, Santiago-Rodriguez E, Ricardo-Garcell J, Fernandez T, Avila-Acosta D. Schizencephaly with occlusion or absence of middle cerebral artery. Neuroradiology 2006;48(3):171-5. PMID 16391916
30: Ferrer I, Catala I. Unlayered polymicrogyria: structural and developmental aspects. Anat Embryol 1991;184:517-28. PMID 1741482
31: Friede RL. Developmental neuropathology. 2nd ed. New York: Springer-Verlag, 1989.
32: Gaines JJ, Gilbert BC, Gossage JR, Parker W, Reddy A, Forsen SE. Schizencephaly in hereditary hemorrhagic telangiectasia. AJNR Am J Neuroradiol 2022;43(11):1603-7. PMID 36265891
33: George E, Vassar R, Mogga A, et al. Spectrum of fetal intraparenchymal hemorrhage in COL4A1/A2-related disorders. Pediatr Neurol 2023;147:63-7. PMID 37562171
34: George E, Vassar R, Tu Y, et al. Fetal MRI findings, etiology, and outcome in prenatally diagnosed schizencephaly. Am J Neuroradiol 2024;A8523.
35: Ghosn Y, Kamareddine MH, Adem C, Jabbour R. A patient with schizencephaly and agenesis of corpus callosum with no neurological deficits. J Neurosci Rural Pract 2018;9(3):404-5. PMID 30069099
36: Gould DB, Phalan FC, Breedveld GJ, et al. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science 2005;308:1167-71. PMID 15905400
37: Gonzalez JC, Singhapakdi K, Martino AM, Rimawi BH, Bhat R. Unilateral open-lip schizencephaly with tonsillar herniation in a preterm infant. J Pediatr Neurosci 2019;14(4):225-7. PMID 31908665
38: Granata T, Battaglia G, D'Incerti L, et al. Schizencephaly: clinical findings. In: Guerrini R, Andermann F, Canapicchi R. Dysplasias of cerebral cortex and epilepsy. Philadelphia: Lippincot-Raven, 1996a:407-15.
39: Granata T, Battaglia G, D'Incerti L, et al. Schizencephaly: neuroradiologic and epileptologic findings. Epilepsia 1996b;37(12):1185-93. PMID 8956850
40: Granata T, Farina L, Faiella A, et al. Familial schizencephaly associated with EMX2 mutation. Neurology 1997;48(5):1403-6. PMID 9153481
41: Granata T, Freri E, Caccia C, Setola V, Taroni F, Battaglia G. Schizencephaly: clinical spectrum, epilepsy, and pathogenesis. J Child Neurol 2005;20:313-8. PMID 15921232
42: Goez H, Zelnik N. Schizencephaly in infants with thrombophilia. J Child Neurol 2009;24(4):421-4. PMID 19168828
43: Griffiths PD. Schizencephaly revisited. Neuroradiology 2018;60(9):945-60. PMID 30027296
44: Guerrini R, Dobyns WB. Malformations of cortical development: clinical features and genetic causes. Lancet Neurol 2014;13(7):710-26. PMID 24932993
45: Gul A, Gungorduk K, Yildirim G, Gedikbasi A, Ceylan Y. Prenatal diagnosis of porencephaly secondary to maternal carbon monoxide poisoning. Arch Gynecol Obstet 2009;279(5):697-700. PMID 18777036
46: Gutierrez-Castillo A, Jiménez-Ruiz A, Chávez-Castillo M, Ruiz-Sandoval J. Septo-optic dysplasia plus syndrome. Cureus 2018;10(12):e3727. PMID 30800538
47: Guzeva VI, Okhrim IV, Guzeva OV, Guzeva VV, Kasumov VR. Kliniko-funktsional'nye narusheniya u patsientov s epilepsiei pri shizentsefalii [Clinical and functional disturbances in epilepsy patients with schizencephaly]. [Russian.] Zh Nevrol Psikhiatr Im S S Korsakova 2023;123(3):46-50. PMID 36946396
48: Hakimi T, Qasem KM. Bilateral open lip schizencephaly. Ann Med Surg (Lond) 2022:73:103204. PMID 35079358
49: Han X, Cheng J, Surapaneni K, Altschuler EL. Schizencephaly: Dramatic images in a normally functioning adult. PM R 2015;7(8):1-2. PMID 25828202
50: Hayashi N, Tsutsumi Y, Barkovich AJ. Morphological features and associated anomalies of schizencephaly in the clinical population: detailed analysis of MR images. Neuroradiology 2002;44:418-27. PMID 12012128
51: Hino-Fukuyo N, Togashi N, Takahashi R, et al. Neuroepidemiology of porencephaly, schizencephaly, and hydranencephaly in Miyagi Prefecture, Japan. Pediatric Neurol 2016;54:39-42. PMID 26545857
52: Hung JH, Shen SH, Guo WY, et al. Prenatal diagnosis of schizencephaly with septo-optic dysplasia by ultrasound and magnetic resonance imaging. J Obstet Gynaecol Res 2008;34(4 Pt 2):674-9. PMID 18840179
53: Iannetti P, Nigro G, Spalice A, Faiella A, Boncinelli E. Cytomegalovirus infection and schizencephaly: case reports. Ann Neurol 1998;43:123-7. PMID 9450779
54: Inan C, Sayin NC, Gurkan H, et al. Schizencephaly accompanied by occipital encephalocele and deletion of chromosome 22q13.32: a case report. Fetal Pediatr Pathol 2019;1-7. PMID 31130048
55: Jansen AC, Robitaille Y, Honavar M, et al. The histopathology of polymicrogyria: a series of 71 brain autopsy studies. Dev Med Child Neurol 2016;58(1):39-48. PMID 26179148
56: Janszky J, Ebner A, Kruse B, et al. Functional organization of the brain with malformations of cortical development. Ann Neurol. 2003;53(6):759-67. PMID 12783422
57: Jbili N, Mounir K, Kechna H, et al. A rare case of super-refractory epileptic status in pregnant woman: schizencephaly. Anaesth Crit Care Pain Med 2019;38(2):195-8. PMID 30012509
58: Khadka C, Gupta U, Bhandari P, Pandey P, Paudel S. A case of closedlip schizencephaly with absent septum pellucidum in an adult presenting with seizure disorder. Clin Case Rep 2023;11(6):e7536. PMID 37323273
59: Khalid R, Krishnan P, Andres K, et al. COL4A1 and fetal vascular origins of schizencephaly. Neurology 2018;90(5):232-4. PMID 29282339
60: Kim DH, Kwon OY, Jung SW, et al. Location of irritative zone in epileptic brains of schizencephalic patients. Clin EEG Neurosci 2016;47(3):235-42.** PMID 25253435
61: Kim YH, Jang SH, Han BS, et al. Ipsilateral motor pathway confirmed by diffusion tensor tractography in a patient with schizencephaly. Neuroreport 2004;15:1899-902. PMID 15305133
62: Kopyta I, Jamroz E, Kluczewska E, Sarecka-Hujar B. Clinical and radiologic features of unilateral and bilateral schizencephaly in polish pediatric patients. J Child Neurol 2014;29(4):442-9. PMID 23503883
63: Kopyta I, Skrzypek M, Raczkiewicz D, Bojar I, Sarecka-Hujar B. Epilepsy in paediatric patients with schizencephaly. Ann Agric Environ Med 2020;27(2):279-83. PMID 32588606
64: Kumar KK, Toland A, Fischbein N, et al. Vascular anomaly, lipoma, and polymicrogyria associated with schizencephaly: developmental and diagnostic insights. Illustrative case. J Neurosurg Case Lessons 2023;5(21):CASE2388. PMID 37218736
65: Kutuk MS, Gorkem SB, Bayram A, Doganay S, Canpolat M, Basbug M. Prenatal diagnosis and postnatal outcome of schizencephaly. J Child Neurol 2015;30(10):1388-94. PMID 25535059
66: Kwon M, Shim WH, Kim MJ, Kim SJ, Lee JH. Dissociative language representation in a patient with schizencephaly. Eur Neurol 2020;83(5):534-5. PMID 33032283
67: Laasri K, Naggar A, El Houss S, et al. Schizencephaly: a rare cause of late-onset epilepsy in an adult. Radiol Case Rep 2023;18(11):3861-4. PMID 37670925
68: Landrieu P, Lacroix C. Schizencephaly: consequence of a developmental vasculopathy. A clinicopathological report. Clin Neuropathol 1994;13:192-6. PMID 7955664
69: LeBlanc R, Tampieri D, Robitaille Y, Feindel W, Andermann F. Surgical treatment of intractable epilepsy associated with schizencephaly. Neurosurgery 1991;29:421-9. PMID 1922710
70: Lee HK, Kim JS, Hwang YM, et al. Location of the primary motor cortex in schizencephaly. AJNR Am J Neuroradiol 1999;20(1):163-6. PMID 9974075
71: Leventer RJ, Phelan EM, Coleman LT, Kean MJ, Jackson GD, Harvey AS. Clinical and imaging features of cortical malformations in childhood. Neurology 1999;53:715-22. PMID 10489031
72: Liang JS, Chien YH, Hwu WL, Yeh SJ, Peng SF. Schizencephaly in LEOPARD syndrome. Pediatr Neurol 2009;41(1):71-3. PMID 19520282
73: Liu PC, Chen HH, Chou CC, et al. Stereo-EEG for epileptogenic focus localization in schizencephaly: a single-center experience in four patients. World Neurosurg 2023;172:e319-25. PMID 36632895
74: Lopes CF, Cendes F, Piovesana AM, et al. Epileptic features of patients with unilateral and bilateral schizencephaly. J Child Neurol 2006;21(9):757-60. PMID 16970881
75: Lubinsky M, Encha-Razavi F. Delineating septo-optic dysplasia. Birth Defects Res 2022;114(20):1343-53. PMID 36200678
76: Maeda T, Akaishi M, Shimizu M, et al. The subclassification of schizencephaly and its clinical characterization. Brain Dev 2009;31(9):694-701. PMID 19038511
77: Matsumoto T, Miyakoshi K, Fukutake M, Ochiai D, Minegishi K, Tanaka M. Intracranial sonographic features demonstrating in utero development of hemorrhagic brain damage leading to schizencephaly-associated COL4A1 mutation. J Med Ultrason 2015;42(3):445-6. PMID 26576802
78: Mellado C, Poduri A, Gleason D, et al. Candidate gene sequencing of LHX2, HESX1, and SOX2 in a large schizencephaly cohort. Am J Med Genet A 2010;152A(11):2736-42. PMID 20949537
79: Mequanint MB, Mengesha CA, Alemu HT, Molla YD. Open lip schizencephaly: an unusual cause of hemiparesis: a case report. Radiol Case Rep 2024;19(11):5354-58. PMID 39280747
80: Merello E, Swanson E, De Marco P, et al. No major role for the EMX2 gene in schizencephaly. Am J Med Genet A 2008;146A(9):1142-50. PMID 18409201
81: Miller SP, Shevell MI, Patenaude Y, Poulin C, O'Gorman AM. Septo-optic dysplasia plus: a spectrum of malformations of cortical development. Neurology 2000;54:1701-3. PMID 10762523
82: Morioka T, Nishio S, Sasaki M, et al. Functional imaging in schizencephaly using [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and single photon emission computed tomography with technetium-99m-hexamethyl-propyleneamine oxime (HMPAO-SPECT). Neurosurg Rev 1999;22(2-3):99-101. PMID 10547006
83: Nabavizadeh SA, Zarnow D, Bilaniuk LT, Schwartz ES, Zimmerman RA, Vossough A. Correlation of prenatal and postnatal MRI findings in schizencephaly. AJNR Am J Neuroradiol 2014;35(7):418-24.** PMID 24610904
84: Nagai Y, Fujimoto A, Okanishi T, et al. Successful hemispherotomy for a patient with intractable epilepsy secondary to bilateral congenital brain malformation with lateralized pyramidal tract of diffusion tensor image tractography. Epilepsy Behav Case Rep 2016;6:30-2. PMID 27453818
85: Oh KY, Kennedy AM, Frias AE Jr, Byrne JL. Fetal schizencephaly: pre- and postnatal imaging with a review of the clinical manifestations. Radiographics 2005;25(3):647-57. PMID 15888615
86: Packard AM, Miller VS, Delgado MR. Schizencephaly: correlations of clinical and radiologic features. Neurology 1997;48:1427-34. PMID 9153485
87: Patwal R, Pai NM, Ganjekar S, et al. Schizencephaly and the neurodevelopmental model of psychosis. Neurol India 2022;70(2):740-3. PMID 35532651
88: Paudel K, Prasad T, Gyawali P, Nepal G, Jaiswal V. Schizencephaly diagnosed after an episode of seizure during labor: a case report. Clin Case Rep 2023;11(5):e7328. PMID 37151943
89: Pooh RK, Machida M, Nakamura T, et al. Increased Sylvian fissure angle as early sonographic sign of malformation of cortical development. Ultrasound Obstet Gynecol 2019;54(2):199-206. PMID 30381845
90: Poretti A, Leventer RJ, Cowan FM, et al. Cerebellar cleft: a form of prenatal cerebellar disruption. Neuropediatrics 2008;39(2):106-12. PMID 18671186
91: Rama Rao R, Reddy AB, Dhanushia P, Koul A. Schizencephaly associated with bipolar affective disorder. Cureus 2024;16(2):e54534. PMID 38516433
92: Richman DP, Stewart RM, Caviness VS. Cerebral microgyria in a 27 week fetus: an architectonic and topographic analysis. J Neuropathol Exp Neurol 1974;33:374-84. PMID 4835115
93: Romaniello R, Arrigoni F, Bassi MT, Borgatti R. Mutations in α- and β-tubulin encoding genes: implications in brain malformations. Brain Dev 2015;37(3):273-80. PMID 25008804
94: Samanta D. Contactin-associated protein-like (CNTNAP) 2 gene mutation in a patient with bilateral schizencephaly. Acta Neurol Belg 2017;117(1):403-4. PMID 27233939
95: Sarnat HB. Cerebral dysgenesis. Embryology and clinical expression. New York: Oxford University Press, 1992.
96: Sarnat HB, Flores-Sarnat L. Telencephalic flexure and malformations of the lateral cerebral (sylvian) fissure. Pediatr Neurol 2016;63:23-38. PMID 27590993
97: Sarnat HB, Flores-Sarnat L. Olfactory development, part 2: Neuroanatomic maturation and dysgeneses. J Child Neurol 2017;32(6):579-92. PMID 28424008
98: Sato Y, Shibasaki J, Aida N, et al. Novel COL4A1 mutation in a fetus with early prenatal onset of schizencephaly. Hum Genome Var 2018;5:4. PMID 29760938
99: Shin C, Nam Kwon Y, Lee D, Ahn TB. Incongruent hemiatrophy and hemiparkinsonism in a patient with schizencephaly. Clin Neurol Neurosurg 2018;175:106-7. PMID 30390483
100: Smigiel R, Cabala M, Jakubiak A, et al. Novel COL4A1 mutation in an infant with severe dysmorphic syndrome with schizencephaly, periventricular calcifications, and cataract resembling congenital infection. Birth Defects Res A Clin Mol Teratol 2016;106(4):304-7. PMID 26879631
101: Spreer J, Dietz M, Raab P, Arnold S, Klisch J, Lanfermann H. Functional MRI of language-related activation in left frontal schizencephaly. J Comput Assist Tomogr 2000;24:732-4. PMID 11045694
102: Squier W, Jansen A. Polymicrogyria: pathology, fetal origins and mechanisms. Acta Neuropathol Commun 2014;2:80. PMID 25047116
103: Sunilkumar D, Nagarajan K, Kiran M, Manjubashini D, Sabarish S. Persistent falcine sinus with temporo-occipital schizencephaly: case report with a review of literature in relation to the undeveloped vein of Galen and/or straight sinus. Childs Nerv Syst 2020;36(2):417-21. PMID 31154486
104: Szczaluba K, Mierzewska H, Obersztyn E, et al. Nijmegen breakage syndrome with macrocephaly, schizencephaly and large CSF spaces--extended spectrum of the condition. J Appl Genet 2012;53(2):189-91. PMID 22293976
105: Takano T, Takikita S, Shimada M. Experimental schizencephaly induced by Kilham strain of mumps virus: pathogenesis of cleft formation. Neuroreport 1999;10:3149-54. PMID 10574551
106: Tanwir A, Bukhari S, Shamim MS. Frontoethmoidal encephalocele presenting in concert with schizencephaly. Surg Neurol Int 2018;9:246. PMID 30603230
107: Tietjen I, Bodell A, Apse K, et al. Comprehensive EMX2 genotyping of a large schizencephaly case series. Am J Med Genet A 2007;143(12):1313-6. PMID 17506092
108: Tietjen I, Erdogan F, Currier S, et al. EMX2-independent familial schizencephaly: clinical and genetic analyses. Am J Med Genet 2005;135:166-70. PMID 15887302
109: Tyls F, Brunovsky M, Sulcova K, Kohutova B, Rynzarova Z, Kopecek M. Latent schizencephaly with psychotic phenotype or schizophrenia with schizencephaly? A case report and review of the literature. Clin EEG Neurosci 2019;50(1):13-9. PMID 29914267
110: Vandermeeren Y, De Volder A, Bastings E, et al. Functional relevance of abnormal fMRI activation pattern after unilateral schizencephaly. Neuroreport 2002;13(14):1821-4. PMID 12395132
111: Veerapaneni P, Veerapaneni KD, Yadala S. Schizencephaly. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing, 2020.
112: Vitale G, Pichiecchio A, Ormitti F, et al. Cortical malformations and COL4A1 mutation: three new cases. Eur J Paediatr Neurol 2019;23(3):410-7. PMID 30837194
113: Vucurovic K, Emeriau S, Coulon JM, et al. Functional brain neuroimaging-guided repetitive transcranial magnetic stimulation in neurodevelopmental disorders: the case of a schizencephaly-related spastic dystonia. J Neurol Sci 2017;378(9):167-9. PMID 28566157
114: Watanabe J, Okamoto K, Ohashi T, et al. Malignant hyperthermia and cerebral venous sinus thrombosis after ventriculoperitoneal shunt in infant with schizencephaly and COL4A1 mutation. World Neurosurg 2019;127:446-50. PMID 31029817
115: Wu YW, Lindan CE, Henning LH, et al. Neuroimaging abnormalities in infants with congenital hemiparesis. Pediatr Neurol 2006;35(3):191-6. PMID 16939859
116: Yakovlev P, Wadsworth RC. Schizencephalies: a study of the congenital clefts in the cerebral mantle, I: clefts with fused lips. J Neuropath Exp Neurol 1946a;5:116-30. PMID 21026933
117: Yakovlev P, Wadsworth RC. Schizencephalies: a study of the congenital clefts in the cerebral mantle, II: clefts with hydrocephalus and lips separated. J Neuropath Exp Neurol 1946b;5:169-206. PMID 21026933
118: Yoneda Y, Haginoya K, Kato M, et al. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Ann Neurol 2013;73(1):48-57. PMID 23225343

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Harvey B Sarnat MS MD FRCPC

Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.
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Former Authors

Geoffrey Miller MD
Giorgio Stefano Battaglia MD
Adele Finardi MD
Tiziana Granata MD
Peter G Barth MD PhD

Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: male=female
Heredity: heredity may be obtained
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-10: Other specified congenital malformations of brain: Q04.8
ICD-11: Schizencephaly: LA05.61
OMIM: Empty Spiracles, Drosophila 2, Homolog of EMX2: *600035

Porencephaly, familial: #175780

Schizencephaly: #269160

Septo-optic dysplasia: #182230

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Schizencephaly

Associated Disorders

Absence of septum pellucidum
Optic nerve hypoplasia
Polymicrogyria
Septo-optic-pituitary dysplasia

Differential Diagnosis

encephaloclastic porencephaly
hydranencephaly
pachygyria

Also Relevant

Cerebral palsy
Microcephaly
Porencephaly
Septo-optic-pituitary dysplasia complex

Clinical Categories

Developmental Malformations

Schizencephaly …

Schizencephaly

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Special considerations

Pregnancy

Media

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

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to access the full version.

Questions or Comment?

Also in This Category

X-linked hydrocephalus (L1 syndrome)

Cerebro-oculo-facio-skeletal syndrome

Fetal anticonvulsant syndrome

Rhombencephalosynapsis

Malformations of the brain

Von Hippel-Lindau disease

Vein of Galen malformations

Mobius syndrome

Schizencephaly

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Special considerations

Pregnancy

Media

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

X-linked hydrocephalus (L1 syndrome)

Cerebro-oculo-facio-skeletal syndrome

Fetal anticonvulsant syndrome

Rhombencephalosynapsis

Malformations of the brain

Von Hippel-Lindau disease

Vein of Galen malformations

Mobius syndrome

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