Schizencephaly () is a rare

birth defect A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

characterized by abnormal clefts lined with

grey matter Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and capillaries. Grey matter is distingui ...

that form the

ependyma The ependyma is the thin Neuroepithelial cell, neuroepithelial (Simple columnar epithelium, simple columnar ciliated epithelium) lining of the ventricular system of the brain and the central canal of the spinal cord. The ependyma is one of the fou ...

of the cerebral ventricles to the

pia mater Pia mater ( or ),Entry "pia mater"
in
epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

, motor deficits, and psychomotor retardation.

Presentation

Schizencephaly can be distinguished from

porencephaly Porencephaly is an extremely rare cephalic disorder involving encephalomalacia. It is a neurological disorder of the central nervous system characterized by cysts or cavities within the cerebral hemisphere.Parker, J. (2004). The official parent ...

by the fact that in schizencephaly, the fluid-filled component is entirely lined by heterotopic grey matter, while a porencephalic cyst is lined mostly by

white matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribution ...

. Individuals with clefts in both hemispheres, or bilateral clefts, are often developmentally delayed and have delayed speech and

language Language is a structured system of communication. The structure of a language is its grammar and the free components are its vocabulary. Languages are the primary means by which humans communicate, and may be conveyed through a variety of met ...

skills and

corticospinal The pyramidal tracts include both the corticobulbar tract and the corticospinal tract. These are aggregations of efferent nerve fibers from the upper motor neurons that travel from the cerebral cortex and terminate either in the brainstem (''co ...

dysfunction. Individuals with smaller, unilateral clefts (clefts in one hemisphere) may be weak or paralyzed on one side of the body and may have average or near-average intelligence. Patients with schizencephaly may also have varying degrees of

microcephaly Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...

Cognitive impairment Cognitive deficit is an inclusive term to describe any characteristic that acts as a barrier to the cognition process. The term may describe * deficits in overall intelligence (as with intellectual disabilities), * specific and restricted defici ...

hemiparesis Hemiparesis, or unilateral paresis, is weakness of one entire side of the body (''wikt:hemi-#Prefix, hemi-'' means "half"). Hemiplegia is, in its most severe form, complete paralysis of half of the body. Hemiparesis and hemiplegia can be caused ...

(weakness or paralysis affecting one side of the body), or

quadriparesis Tetraplegia, also known as quadriplegia, is defined as the dysfunction or loss of motor and/or sensory function in the cervical area of the spinal cord. A loss of motor function can present as either weakness or paralysis leading to partial or t ...

(weakness or paralysis affecting all four extremities), and may have reduced muscle tone (hypotonia). Most patients have seizures, and some may have

hydrocephalus Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...

Causes

In schizencephaly, the neurons border the edge of the cleft, implying a very early disruption of the usual grey matter migration during embryogenesis. The cause of the disruption is not known, but likely the cause may be either genetic or a physical insult, such as infection, infarction, hemorrhage, in utero stroke, exposure to a toxin, or mutation. It is thought that normal neuron migration during the second trimester of intrauterine development, when primitive neuron precursors (germinal matrix) migrate from just beneath the ventricular ependyma to the peripheral hemispheres

where Where may refer to: * Where?, one of the Five Ws in journalism * where (command), a shell command * Where (SQL), a database language clause * Where.com Where, Inc. was a location-based media company in North America. Their main products were ...

they form the cortical grey matter.

Genetic

There was once thought to be a genetic association with the ''

EMX2 Homeobox protein Emx2 is a protein that in humans is encoded by the ''EMX2'' gene. Function The homeodomain transcription factor EMX2 is critical for central nervous system and urogenital development. EMX1 (MIM 600034) and EMX2 are related to ...

'' gene, although this theory has recently lost support. However it has been confirmed that mutations in the ''

COL4A1 Collagen alpha-1(IV) chain (COL4A1) is a protein that in humans is encoded by the ''COL4A1'' gene on chromosome 13. It is ubiquitously expressed in many tissues and cell types. COL4A1 is a subunit of the type IV collagen and plays a role in angiog ...

'' gene occur in some patients with schizencephaly.

In utero infections

Schizencephaly may also be caused by environmental toxin exposure during pregnancy, infection during pregnancy (such as

Cytomegalovirus ''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...

), or a vascular insult. Often there are additional associated heterotopias (isolated islands of neurons) which indicate a failure of migration of the neurons to their final position in the brain caused by possible stroke.

Diagnosis

* Radiological methods like computed tomography (CT) and/or

magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...

(MRI) - unilateral or bilateral clefting of the brain. * Genetic testing for confirmation of mutations in the genes associated with susceptibility to the condition.

Treatment

Treatment for individuals with schizencephaly generally consists of physical therapy (KG-ZNS with Vojta Methode), occupational therapy (with specific emphasis on neuro-developmental therapy techniques), treatment for seizures, and, in cases that are complicated by hydrocephalus, a shunt.

Prognosis

The prognosis for individuals with schizencephaly varies depending on the size of the clefts and the degree of neurological deficit.

Frequency

In some cases, the defect is linked to mutations of the

SIX3 Homeobox protein SIX3 is a protein that in humans is encoded by the ''SIX3'' gene. Function The SIX homeobox 3 (SIX3) gene is crucial in embryonic development by providing necessary instructions for the formation of the forebrain and eye deve ...

, and

Collagen, type IV, alpha 1 Collagen alpha-1(IV) chain (COL4A1) is a protein that in humans is encoded by the ''COL4A1'' gene on chromosome 13. It is ubiquitously expressed in many tissues and cell types. COL4A1 is a subunit of the type IV collagen and plays a role in angiog ...

genes. Because having a sibling with schizencephaly has been statistically shown to increase risk of the disorder, it is possible that there is a heritable genetic component to the disease.

References

9.^ Herrera Ortiz, A., & Ortiz Sandoval, H. (2021). Open Lip Schizencephaly: A Case Report. Revista Cuarzo, 26(2), 27-29. https://doi.org/10.26752/cuarzo.v26.n2.510

External links

*
OMIM entries on Familial Schizencephaly, SIX3-Related
{{Congenital malformations and deformations of nervous system Congenital disorders of nervous system Rare diseases