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The central nervous system (CNS) is the most complex organ in the human body comprising a highly organized anatomic scaffold of billions of cells and a network of trillions of connections. Structural brain development proceeds through an integrated series of often rapid developmental events from early embryogenesis through fetal life and into early adulthood. It is therefore not surprising that many common childhood neurologic and developmental disorders have their origins in genetic or environmental perturbations of embryonic or fetal brain development.

Advances in genetics and diagnostic imaging, including prenatal imaging, have led to earlier and more complete diagnosis and enhanced prognostication for CNS malformations and the ability to counsel effectively regarding recurrence. The diagnosis of malformations has been revolutionized by magnetic resonance imaging (MRI), and the challenge for the pediatrician is often to translate the imaging diagnosis to effectively counsel the family and plan further care and management for the child. Modern neonatal neurologic and neurosurgical intensive care together with progress in early intervention and pediatric rehabilitation means children with malformations of the brain or spinal cord may now survive longer and with improved quality of life.

Malformations of the CNS are among the most common problems in child neurology. Brain development is abnormal in an estimated 25% of conceptions and is responsible for a high percentage of miscarriage and stillbirth. Brain malformations are, together with congenital heart disease, the leading cause of neonatal and postneonatal mortality in the developed world. Brain malformations are after cerebral palsy, the leading cause of childhood morbidity and mortality related primarily to consequent neurologic disability and epilepsy. Brain malformations frequently coexist with other malformations of organ systems, in particular the eye, heart, kidneys, gut, and skeleton.

The neuraxis develops following the fate decision of several early embryonic cells to become neural progenitors and by the second week of embryogenesis the three primary layers of ectoderm, mesoderm, and endoderm are formed. It subsequently proceeds through the dorsal and ventral induction to form the neural tube, lower spinal cord and eventually the prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon (hindbrain). This is followed by massive cellular proliferation of both neuronal and glial precursors and later differentiation into specific neuronal and glial types. Cortical development occurs with migration of neuronal and glial precursors away from the ventricular and subventricular zone towards the pial surface to form the neocortex and major commissures such as the corpus callosum. This is followed by cortical organization that includes alignment, orientation, and layering of cortical neurons together with synaptogenesis. From the end of the second trimester into early childhood late glial differentiation and myelination, together with programmed and experience-dependent synaptic formation and pruning predominate.

The range of known malformations is almost as complex as the series of developmental events that lead to the formation of the brain. They are perhaps best understood as the effects of insults—regardless of type—at key points in the development of the brain. Although ...

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