An article describing the brain disorder Lissencephaly, the differences in genetic development between a normal and smooth brain and siezure management.
The term lissencephaly simply means 'smooth brain', derived from the Greek words for smooth (lissos) and brain (enkephalos). This was initially described about 100 years ago[1]. Classical lissencephaly, is a severe irregularity of neuronal migration which is characterised by absent cerebral convolutions (agyria) or abnormally broad/decreased surface convolutions (pachygyria) leading to the production of a smooth cerebral surface. In this condition it is found that the cerebral cortex is unusually thick, measuring 10-15 mm in contrast to the normal width of 2-3 mm. The cytoarchitecture is noticeably abnormal, in that it consists of only four layers including an outer marginal layer, a superficial cellular layer which corresponds to the true cortex, a variable cell sparse layer, and a deep cellular layer made of heterotopic neurons which extends more than half the width of the mantle.
Lissencephaly is also characterized by enlarged lateral ventricles without hydrocephalus, while the corpus callosum is often abnormal in shape, small or dysmorphic. Other abnormalities include hypoplasia of the corticospinal tracts, and mild dysplasia of the cerebellar cortex. The head circumference at birth is normal or only slightly smaller.
Lissencephaly is a brain disorder in which neurones are unable to stop at the marginal zone due to disruption of the early migration pattern of neurons, and so they migrate through the marginal zone into the subarachnoid space.
A gene on chromosome 17 was isolated and was named LIS1 in 1993[2]. It was discovered that children with lissencephaly had one less copy of this gene because of a microdeletion. The protein that is encoded by that gene is either shortened or entirely missing, depending on the size of the deletion of the gene. In children with isolated lissencephaly, the deletions are small and contained within the LIS1 gene. In children with the more severe MDS, the deletions are larger and they extend beyond the boundaries of the LIS1 gene.
It is as yet unclear whether the LIS1 gene is required for the initiation of migration, for the successful migration of neurons through the cortical layers, or for some other step in the process by which neurons find their ultimate destination.
Seizures can damage alertness and can cause additional injury in children. It has been found that most children suffering from lissencephaly can be helped by seizure medicines. Good seizure control will not lessen or affect in any way the mental retardation which accompanies children with complete lissencephaly, but poor seizure control can make their function worse. Regression associated with seizures can often improve if seizure control is improved. Children with poor seizure control are usually less alert and have less control over swallowing. They are more likely to aspirate than children with fewer seizures. Aspiration can cause pneumonia or even sudden death.
It is well known that malnutrition during the first two years of a childs life can impair both motor and cognitive development, so correct nutritional care will help children with disabilities reach their full potential.
[1] Matell M (1893) Arch Psychiatr Nervenkr 25:124-136
[2] Dobyns WB, Reiner O, Carrozzo R, Ledbetter DH (1993), Lissencephaly: a human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13. JAMA 270:2838 - 2842
