Synonyms and Historical Annotations

Chapter 4. Lissencephaly, Type I 35 DEFINITION Lissencephaly, derived from the Greek works “lissos” meaning smooth and “enkephalos” which means brain, is a descriptive term defining a class of human cerebral malformations characterized by the agyric surface of the brain. In fact, most cases of lissencephaly do not have a complete loss of gyri; often the most ventral and medial gyri are relatively spared along with other brain regions that are variable preserved depending on the specific genetic mutation. e underlying defect in lissencephaly is a defect in cell migration. Cell migration has been implicated in many disorders (chapters 5, 6, 7, 9); however, lissencephaly, along with heterotopia, are the only disorders that are clearly pathogenetically proven to be cell migration defects. Resulting from a slowing or delay in cell migration and not an absolute loss of movement, a second hallmark of lissencephaly is a thickening of the cerebral cortex. In addition to the absence of gyri and the thickening of the cerebral cortex, brains from patients with lissencephaly may show a variety of associated malformation. Lissencephaly is not a single malformation, but a descriptive term applied to many malformations with distinct genetic etiologies. is chapter will focus on the lissencephalies associated with a failure in normal cell migration as opposed to the next chapter that will examine the lissencephalies resulting from an apparent over migration of neurons (chapter 5). Heterotopia, also a migration disorder, will be addressed in chapter 7. e lissencephalies described in this chapter have also been referred to as type I lissencephaly or classical lissencephaly. For the purposes of this chapter these disorders will be defined as type I lissencephaly. As the genetic basis of lissencephaly continues to be delineated, these definitions will likely evolve to include specific genetic defects.