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Schizencephaly is a rare congenital cerebral malformation characterized by the presence of linear clefts in one or both hemispheres of the brain, extending from the lateral ventricles to the pial surface of the cortex, and that lead to a variety of neurological symptoms such as epilepsy, motor deficits, and psychomotor retardation.
The prevalence is estimated at 1/64,935 births in the USA and 1/69,444 in UK.
Patients with schizencephaly have varying clinical features including epilepsy (50-60% of cases), motor impairment, microcephaly and cognitive and learning disability. The severity of the clinical manifestations depends upon the extent of clefting and on whether other cerebral malformations are present. When a cleft affects one hemisphere alone (unilateral clefts), patients can have a hemiparesis but they may have little or no intellectual disability. Patients with bilateral clefts have a more severe phenotype that may be characterized by severe developmental impairment with spastic quadriplegia and severe intellectual disability. Schizencephaly is often associated with septo-optic dysplasia (see this term).
Schizencephaly results from an acquired defect of the cerebral mantle usually becoming apparent only in the second half of pregnancy. Schizencephaly has been linked to a young maternal age and to conditions secondary to vascular disruption such as maternal drug administration (e.g. warfarin), amniocentesis, and infections (cytomegalovirus). Recently, mutations in the COL4A1 gene encoding the major type IV alpha collagen chain of basement membranes have been found responsible of some schizencephaly cases. Other genetic factors have been suggested to play a role in its pathogenesis, such as EMX2, SHH, and SIX3 that could act as susceptibility factors.
Postnatally, the diagnosis is made by computed tomography (CT) and/or magnetic resonance imaging (MRI) showing unilateral or bilateral clefting of the brain. Clefts are surrounded by gray matter and are often associated with polymicrogyria and/or pachygyria on the sides. Clefts are referred to as closed-lip (type I) when the tissue surrounding the clefts is fused, and open-lip (type II) when the tissue is separated by cerebrospinal fluid. Cerebral malformations that can be associated with schizencephaly (observed by brain imagery) include optic nerve hypoplasia, hydrocephalus, absence of corpus callosum or septum pellucidum, cerebellar hypoplasia, or calcifications. Genetic testing will confirm mutations in the genes associated with susceptibility to the condition.
Differential diagnosis includes porencephaly (see this term).
Prenatal diagnosis is made after 20 weeks of pregnancy by ultrasound examination demonstrating clefting of the cerebral mantle. The diagnosis may be confirmed by MRI, which may give additional information about the presence of septo-optic dysplasia.
Most cases are sporadic but some familial cases have also been observed with inheritance reported to be either autosomal recessive or autosomal dominant with variable penetrance.
Management and treatment
Treatment consists on administration of anti-epileptic drugs in order to prevent seizures. In drug resistant cases (1/3rd of cases), surgery (e.g. resection of either the schizencephalic cleft alone or the cleft and surrounding epileptogenic tissue, temporal or frontotemporal lobectomy) can be performed. A regular neurologic evaluation is necessary. Physical and occupational therapy are essential.
The prognosis is variable and depends on the degree of clefting and the association with other cerebral malformations. Individuals with schizencephaly can have features of a hemiparesis only but the clinical picture can extend to profound neurological impairment with spastic quadriplegia leading to immobility and to severe learning disability and epilepsy.
- Summary information
- Suomi (2014, pdf)