Classification system for malformations of cortical development

The classification system for malformations of cortical development organizes myriad conditions into one of three major underlying groups according to the main underlying mechanism:

• group I: abnormal cell proliferation or apoptosis
• group II: abnormal neuronal migration
• group III: abnormal cortical organization

As is to be expected a number of conditions fall outside these three groupings and are placed in a miscellaneous group: those associated with other diseases or yet to be classified ². The classification present below is a summary with examples adapted from the one proposed by Barkovich et al in 1996 and updated in 2001, 2005 and 2012 ^1-2,5,6. The full classification is extensive, contains numerous rare and specific abnormalities beyond the scope of this or other related articles and will certainly evolve over the coming years. As such you are encouraged, if necessary, to review the most recent (2012) update for further details ⁵. 

Group I: abnormal cell proliferation or apoptosis 

Group 1 conditions include those due to disorders of neuronal and/or glial proliferation or apoptosis. They can be further divided into three groups; those with abnormalities of brain size – A) small and B) large – and C) those with cortical dysgenesis with abnormal cells (neoplastic or non-neoplastic) ².

Group I.A

• microcephaly
  • with normal to simplified cortical pattern 
  • microcephaly with lissencephaly
  • microcephaly with extensive polymicrogyria 

Group I.B

• megalencephaly/macrocephaly

Group I.C

The cortical dysgenesis with abnormal cell proliferation group contains a number of both neoplastic and non-neoplastic conditions. 

Non-neoplastic

• cortical hamartomas of tuberous sclerosis 
• cortical dysplasia with balloon cells 
• hemimegalencephaly
• type II focal cortical dysplasia

Neoplastic

• gangliogliomas 
• gangliocytomas
• dysembryoplastic neuroepithelial tumors (DNET)

Group II: abnormal neuronal migration

Group II.A

• subependymal heterotopia
• marginal glioneuronal heterotopia

Group II.B 

• lissencephaly type I: subcortical band heterotopia spectrum (band heterotopia): under migration
• lissencephaly type II (cobblestone complex): over migration

Group II.C

• subcortical heterotopia (not including band heterotopia)

Group III: abnormal post migrational development

Group III.A

• polymicrogyria and schizencephaly
  • bilateral polymicrogyria syndromes
  • schizencephaly
  • polymicrogyria or schizencephaly as part of multiple congenital anomaly/intellectual disability syndromes​

Group III.B

• cortical dysgenesis secondary to inborn errors of metabolism
  • mitochondrial and pyruvate metabolic disorders
  • peroxisomal disorders

Group III.C

• type I and type III focal cortical dysplasia

Group III.D

• post-migrational microcephaly (also in group I)

Not otherwise classified

• malformations secondary to inborn errors of metabolism
  • mitochondrial and pyruvate metabolic disorders 
  • peroxisomal disorders 
• other unclassified malformations
  • sublobar dysplasia 

See also

For other congenital central nervous system classifications see:

1. classification system for midline abnormalities of the brain
2. classification system for malformations of the cerebellum
3. classification system for malformations of the brainstem