Malformations of cortical development: clinical features and genetic causes

Lancet Neurol. 2014 Jul;13(7):710-26. doi: 10.1016/S1474-4422(14)70040-7. Epub 2014 Jun 2.


Malformations of cortical development are common causes of developmental delay and epilepsy. Some patients have early, severe neurological impairment, but others have epilepsy or unexpected deficits that are detectable only by screening. The rapid evolution of molecular biology, genetics, and imaging has resulted in a substantial increase in knowledge about the development of the cerebral cortex and the number and types of malformations reported. Genetic studies have identified several genes that might disrupt each of the main stages of cell proliferation and specification, neuronal migration, and late cortical organisation. Many of these malformations are caused by de-novo dominant or X-linked mutations occurring in sporadic cases. Genetic testing needs accurate assessment of imaging features, and familial distribution, if any, and can be straightforward in some disorders but requires a complex diagnostic algorithm in others. Because of substantial genotypic and phenotypic heterogeneity for most of these genes, a comprehensive analysis of clinical, imaging, and genetic data is needed to properly define these disorders. Exome sequencing and high-field MRI are rapidly modifying the classification of these disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Proliferation
  • Cerebral Cortex / abnormalities
  • Cerebral Cortex / pathology
  • Developmental Disabilities / epidemiology
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology*
  • Diagnostic Imaging / methods
  • Genetic Testing / methods
  • Humans
  • Malformations of Cortical Development / epidemiology
  • Malformations of Cortical Development / genetics*
  • Malformations of Cortical Development / pathology*
  • Mutation / genetics*