Table 2

Examples of genetic malformations of cortical development

Cortical malformationAssociated features, MRIGene (Inheritance)
Malformation due to abnormal neuronal migration
 LISNo 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 + dysplasiaRELN, VLDR, CDK5 (AR)
Posterior or diffuse LIS, severe cerebellar+brainstem hypoplasiaTUBA1A (AD)
 Subcortical band heterotopiaNo other associated malformation of cortical developmentLIS1 (AD), DCX (XL)
 Bilateral periventricular heterotopiaMRI: Bilateral contiguous nodules, mild cerebellar vermis hypoplasia with mega cisterna magnaFLNA (XL), ARFGEF2 (AR)
 Walker–Warburg syndrome/Muscle-eye-brain diseaseMRI: lack of normal sulcation, frontal predominant cobblestone appearancePOMT1, POMT2 (AR)
Malformations due to abnormal post migrational development
 Bilateral perisylvian polymicrogyria+/– megalencephalyPIK3R2 (AD)*
 Bilateral frontoparietal polymicrogyriaMRI: Cobblestone malformationADGRG1 (AR)
 Polymicrogyria with microcephaly+/– agenesis corpus callosum, cerebellar hypoplasiaTUBA1A (AD), DYNC1H1(AD),RTTN(AR)
Malformations secondary to abnormal cell proliferation
 MegalencephalyNo cortical malformation:
Sotos syndrome†
Weaver’s syndrome‡
Severe megalencephaly with autismWith perisylvian polymicrogyria:
NSD1 (AD)
EZH2 (AD)
PTEN (AD)PIK3CA, PIK3R2, AKT3 (AD)*
 HemimegalencephalyNo other syndromic featuresAKT3 (AD)*
 Focal cortical dysplasia 2a, 2bMRI: cortical thickening, blurring grey/white junction, increased T2/flair signal from cortex to ventricle ‘transmantle sign’AKT3, NPRL3, DEPDC5 (AD, Somatic mutation)*
 Tuberous sclerosisMRI: cortical and subependymal tubers, white matter abnormalitiesTSC1, 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.