Schizencephaly Health Article

Causes and symptoms

The cause of schizencephaly is unknown, although environmental and genetic factors have been proposed. Various theories exist as to the timing and nature of the defect in development. Early injury to the brain during the second trimester of pregnancy has been proposed to cause the characteristic clefts. These insults may be due to infection, poor blood flow causing stroke, or genetic abnormalities. The earlier onset of injury leading to absence of scar tissue around the defect presumably differentiates schizencephaly from porencephaly. A mutation in the EMX2 gene has been associated with schizencephaly in some familial cases, providing evidence for genetic causes. EMX2 is a transcription factor on human chromosome 10 that is important in early brain formation in mice and flies. The clefts in schizencephaly are often lined by normal brain tissue, but may often be surrounded by abnormal brain tissue that has an unusually high density of folding (polymicrogyria). Schizencephaly may also be associated with abnormal nerve clusters called heterotopias in different parts of the brain. Polymicrogyria and heterotopias are thought to be due to defective neuronal migration, and their association with schizencephaly suggests a common underlying mechanism.

Symptoms

Symptoms can vary widely depending on the extent and the size of the cleft. Patients may show developmental delay that can range from mild to severe. Bilateral and open-lip clefts are associated with more severe delay. Affected individuals may have small heads (microcephaly) or increased pressure due to fluid accumulation inside the brain, known as hydrocephalus. Paralysis of the limbs may be present. The paralysis may be on one or both sides of the body depending on the location of the clefts. Abnormal muscle tone, including decreased tone (hypotonia) and increased tone (spasticity), can be seen. Some patients may have only seizures. Seizures usually present before three years of age, but patients may present with seizures in later life as their only symptom and then be diagnosed with schizencephaly by brain imaging.

Diagnosis

Diagnosis is made by imaging of the brain. A computed tomography scan (CT) or MRI demonstrates the abnormal clefts, which may be bilateral or unilateral, open or closed lip. The clefts may appear symmetric or asymmetric. MRI may show evidence of polymicrogyria lining the clefts. There is no genetic testing available at this time for schizencephaly.