Examples of genetic malformations of cortical development
| Cortical malformation | Associated features, MRI | Gene (Inheritance) |
| Malformation due to abnormal neuronal migration | ||
| LIS | No other associated malformation of cortical development MRI: posterior > anterior | LIS1 (AD) more common, DCX (XL) |
| No other associated malformation of cortical development MRI: anterior > posterior | DCX (XL) more common, LIS1 (AD) | |
| Mild frontal LIS. Severe hippocampal, cerebellar hypoplasia + dysplasia | RELN, VLDR, CDK5 (AR) | |
| Posterior or diffuse LIS, severe cerebellar+brainstem hypoplasia | TUBA1A (AD) | |
| Subcortical band heterotopia | No other associated malformation of cortical development | LIS1 (AD), DCX (XL) |
| Bilateral periventricular heterotopia | MRI: Bilateral contiguous nodules, mild cerebellar vermis hypoplasia with mega cisterna magna | FLNA (XL), ARFGEF2 (AR) |
| Walker–Warburg syndrome/Muscle-eye-brain disease | MRI: lack of normal sulcation, frontal predominant cobblestone appearance | POMT1, POMT2 (AR) |
| Malformations due to abnormal post migrational development | ||
| Bilateral perisylvian polymicrogyria | +/– megalencephaly | PIK3R2 (AD)* |
| Bilateral frontoparietal polymicrogyria | MRI: Cobblestone malformation | ADGRG1 (AR) |
| Polymicrogyria with microcephaly | +/– agenesis corpus callosum, cerebellar hypoplasia | TUBA1A (AD), DYNC1H1(AD),RTTN(AR) |
| Malformations secondary to abnormal cell proliferation | ||
| Megalencephaly | No cortical malformation: Sotos syndrome† Weaver’s syndrome‡ Severe megalencephaly with autismWith perisylvian polymicrogyria: |
NSD1 (AD) EZH2 (AD) PTEN (AD)PIK3CA, PIK3R2, AKT3 (AD)* |
| Hemimegalencephaly | No other syndromic features | AKT3 (AD)* |
| Focal cortical dysplasia 2a, 2b | MRI: cortical thickening, blurring grey/white junction, increased T2/flair signal from cortex to ventricle ‘transmantle sign’ | AKT3, NPRL3, DEPDC5 (AD, Somatic mutation)* |
| Tuberous sclerosis | MRI: cortical and subependymal tubers, white matter abnormalities | TSC1, TSC2 (AD) |
*PI3K-AKT-mTOR pathway gene
†Sotos syndrome: macrocephaly, intellectual disability, behavioural problems, seizures.
‡Weavers syndrome: macrocephaly, advanced osseous maturation, distinctive craniofacial features, intellectual disability, behavioural problems, seizures. See also Genetics Home Reference https://ghr.nlm.nih.gov/
LIS, lissencephaly; MEG, megalencephaly.