Genes shown to cause lissencephaly include both autosomal and X-linked genes. Below, the mutations of LIS1 or DCX genes are discussed as they are most commonly linked to neuronal migration disorders including lissencephaly-pachygyria and subcortical band heterotopia. LIS1
LIS1 is responsible for the autosomal form of lissencephaly. Mutations of the LIS1 gene are associated with about 80% of those affected with lissencephaly. LIS1 was the first human neuronal migration gene to be cloned. It is responsible for encoding the alpha subunit of the intracellular Ib isoform of platelet-activating factor acetylhydrolase. It is located on chromosome 17p13.3 and has 11 exons with a coding region of 1233bp. LIS1 protein appears to interact with tubulin to suppress microtubule dynamics. The protein is highly conserved and studies have shown that it participates in cytoplasmic dynein-mediated nucleokinesis, somal translocation, cell motility, mitosis, and chromosome segregation. LIS1 encodes for a 45kDa protein called PAFAH1B1 that contains seven WD40 repeats required for proper neuronal migration. The LIS1 gene encodes for a protein similar to the β subunit of G proteins responsible for degrading bioactive lipid platelet-activating factor (PAF). This leads to theories that LIS1 might exert its effect on migration through microtubules. Specific concentrations of PAF may be necessary for optimal neuronal migration by influencing cell morphology adhesion properties. Studies have shown that addition of PAF or inhibition of platelet-activating factor acetylhydrolase (PAF-AH) decreases cerebellar granule cell migration in vitro. Addition of PAF to hippocampal cells have shown growth cone collapse and neurite retraction.
Hemimegalencephaly (HME), or unilateral megalencephaly, is a rare congenital disorder affecting all or a part of a cerebral hemisphere. It causes severe seizures, which are often frequent and hard to control. A minority might have seizure control with medicines, but most will need removal or disconnection of the affected hemisphere as the best chance. Uncontrolled, they often cause progressive intellectual disability and brain damage and stop development. Symptoms and signs
Seizures are the main symptom. There can be as many as hundreds of seizures a day. Seizures tend to begin soon after birth, but may sometimes commence during later infancy or, rarely, during early childhood. Other symptoms
Asymmetrical or enlarged head
Developmental delay
Progressive weakness of half the body
Progressive blindness of half the body

Genetics
Somatic activation of AKT3 causes hemispheric developmental brain malformations. Pathophysiology
It is a disorder related to excessive neuronal proliferation and hamartomatous overgrowth affecting the cortical formation. The excessive proliferation is postulated to occur early and to possibly continue beyond the normal proliferative period. Epidermal growth factor is thought to play an important role in the excessive proliferation and the pathogenesis of HME. Diagnosis
It should be suspected in infants or children with intractable, frequent seizures. On a CT scan, the affected part is distorted and enlarged. It can be diagnosed prenatally, but a lot of cases go undiagnosed until seizures begin. Ultrasound can display asymmetrical brain hemispheres. Treatment
Although there have been a few reports of medical treatment, the main treatment is radical: remove or disconnect the affected side.