Figure 3.

Diverse human brain malformations. The panel shows axial MRI scans from a normal individual (E) surrounded by MRI scans of brains from 8 individuals with Mendelian disorders of cerebral cortical development. A, perisylvian polymicrogyria, presents with normal patterns of cortical folding frontally and posteriorly, with disrupted gyral folding in the perisylvian region (arrows). These patients have a wide range of intellectual and epilepsy phenotypes from almost normal to severely epileptic and intellectually disabled. B shows bilateral frontoparietal polymicrogyria, reflecting biallelic mutation in GPR56, associated with severe intellectual and motor disability. C shows classical lissencephaly, with a smooth, thick cortex, reflecting abnormal neuronal migration, and associated with intractable neonatal epilepsy, severe motor disability, and usually early death. D shows “double cortex” syndrome, in this case due to a female with heterozygous mutations in the X-linked DCX gene, and again showing a very wide range of phenotypes, generally proportional to the thickness of the abnormal subcortical band of neurons, and including intellectual disability and seizures. F shows Walker-Warbug lissencephaly, also associated with severe disability, intractable epilepsy, and early death. G shows periventricular nodular heterotopia, with the abnormally located neurons highlighted by arrows, and associated with FLNA mutation. This condition is generally associated with normal intelligence and variable seizures, and with some patients being clinically asymptomatic altogether. H shows primary microcephaly, in this case due to biallelic mutation in ASPM, and associated with a cortex that is 50–60% reduced in volume, but relatively normally patterned, with normal cortical thickness, and associated with good motor function, intellectual disability, but usually some language development. I shows a patient with complex microcephaly with simplified and abnormal gyral patterning, in this case reflecting biallelic mutation in WDR62, and associated with more severe intellectual disability and motor delay.