[2] It is caused by defective neuronal migration during the 12th to 24th weeks of gestation, resulting in a lack of development of brain folds (gyri) and grooves (sulci).

Affected children display severe psychomotor impairment, failure to thrive, seizures, and muscle spasticity or hypotonia.

[4] Other symptoms of the disorder may include unusual facial appearance, difficulty swallowing, and anomalies of the hands, fingers, or toes.

This uneven cortical surface is due to incomplete organogenesis which leads to no distinguishable layers in the cerebral cortex.

[5] Causes of lissencephaly can include viral infections of the uterus or the fetus during the first trimester,[6] or insufficient blood supply to the fetal brain early in pregnancy.

[10] The lack of gyri causing a smooth appearance of the cerebral cortex is due to abnormal neuronal migration in the developmental stages of the nervous system.

[12] Mutations in LIS1, DCX (doublecortin), ARX (aristaless related homeobox), RELN have all been identified to cause lissencephaly.

[10] LIS1 is integral in regulating the motor protein dynein which plays an important role in the movement of neuronal nuclei along microtubules.

[15] Miller-Dieker syndrome, however, has additional deletions of adjacent genes on chromosome 17 causing facial and other congenital abnormalities and defects.

[15] This mutation full or deletion of chromosome 17p13.3 leads to inadequate neuronal migration due to LIS1 encoding for an enzyme that interacts with the microtubule protein dynein.

[12] DCX mutation causes the disorganisation of neocortical layering in the cerebral cortex leading to a reduced folding.

[13] As ARX is expressed in the ganglionic eminences and the neocortical ventricular zone it can affect both radial and tangential migration.

In reported cases, lissencephaly caused by RELN deficiency has been more severe in anterior brain regions with a very small cerebellum.

[14] The diagnosis of lissencephaly is usually made at birth or soon after by ultrasound,[19] computed tomography (CT), or magnetic resonance imaging (MRI).

[20] However, these results should be interpreted cautiously since even experienced radiologists can misdiagnose polymicrogyria, a different developmental malformation of the brain, as lissencephaly.

Before birth, complex ultrasounds performed routinely during pregnancy may indicate the presence of a cerebral abnormality, but this method of diagnosis should be complemented by other methods, such as genetic studies and NMR, and the examination is not recommended as part of routine ultrasound examinations, unless family medical history or other reasons for suspecting brain malformation are present.