Schizencephaly: Heterogeneous etiologies in a population of 4 million California births

Abstract

Schizencephaly is a rare congenital brain defect characterized by gray matter lined clefts of the cerebral mantle, frequently accompanied by other defects of the CNS such as absence of the corpus callosum. This study in a California population of >4 million births from 1985-2001 found a population prevalence of 1.54/100,000. Among 63 cases, there was an association with young parental age in isolated schizencephaly (RR 3.9 mothers; 5.8 fathers), which was also seen in mothers but not fathers of non-isolated cases (RR 3.2). Monozygotic twins may also be at increased risk for schizencephaly (RR 2.1). One third of cases had a non-CNS abnormality, over half of which could be classified as secondary to vascular disruption, including gastroschisis, bowel atresias, and amniotic band disruption sequence. Other apparent rare causes included chromosomal aneuploidy, non-random associations, and unusual syndromes. Our observations suggest that schizencephaly has heterogeneous etiologies many of which are vascular disruptive in origin.

Abnormal development of the human cerebral cortex

“…Most cases result from a vascular disruption; attempted abortion, amniocentesis, chorionic villus sampling and motor vehicle accidents have been described in association with the condition. Twenty-three of 43 cases of 'isolated schizencephaly' were bilateral (Curry et al 2005).…”

Correlation of Prenatal and Postnatal MRI Findings in Schizencephaly

“…The etiology of schizencephaly is poorly understood; however, it appears to be heterogeneous. [1][2][3] The presence of gray matter lining the defects, distinguishing schizencephaly from porencephaly, is usually ascribed to the damage to the radial glial cell fibers or to the molecules that promote neuronal migration and timing during pregnancy. 2,4 Despite early reports of the association of schizencephaly and mutations of the EMX2 homeobox gene, 5 this association has not been verified in further studies.…”

“…2,4 Despite early reports of the association of schizencephaly and mutations of the EMX2 homeobox gene, 5 this association has not been verified in further studies. 6 The common pathophysiology of injury is frequently ascribed to a vascular disruption, hypoxia-ischemia, and/or prenatal infection at critical time points during neuronal development, [1][2][3] though there are some reports favoring schizencephaly as a developmental disorder. [7][8][9] Classically, schizencephaly has been divided into "closed" or "closed-lip" defects, in which the walls appose one another within the defect, and "open" or "open-lip" defects, in which CSF fills the defect all the way from the lateral ventricle to the overlying subarachnoid space.…”

Prenatal diagnosis of schizencephaly after inhalation of organic solvents

“…Heterogeneous mutations of the EMX2 gene are reported to give rise to schizencephaly 6 . In addition, cytomegalovirus, abdominal trauma and toxic agents have been reported to be associated with schizencephaly, possibly as the result of a vascular insult 7,8 . Clinical presentation of schizencephaly includes varying degrees of developmental delay, motor impairment and seizures.…”