Neonatology pp 2113-2124 | Cite as

Malformations of Cortical Development in Newborns: Genetic Aspects

  • Renzo GuerriniEmail author
  • Elena Parrini
Reference work entry


The malformations of cortical development (MCD) represent a major cause of developmental disabilities, severe epilepsy, and reproductive disadvantage. Genes that have been associated to MCD are mainly involved in cell proliferation and specification, neuronal migration, and late cortical organization. Lissencephaly-pachygyria-severe band heterotopia are diffuse neuronal migration disorders (NMDs) causing severe, global neurological impairment. Abnormalities of the LIS1, DCX, ARX, and RELN genes have been associated with these malformations. Recent work has also established a relationship of lissencephaly, with or without associated microcephaly, corpus callosum dysgenesis, and cerebellar hypoplasia and, at times, a morphological pattern consistent with polymicrogyria with mutations of several genes (KIF2A, KIF5C, TUBA1A, TUBA8, TUBB, TUBB2B, TUBB3, TUBG1, and DYNC1H1) regulating the synthesis and function of microtubule and centrosome key components and hence defined as tubilinopathies. MCDs only affecting subsets of neurons, such as mild subcortical band heterotopia and periventricular heterotopia, cause neurological and cognitive impairment that vary from severe to mild deficits. They have been associated with abnormalities of the DCX, FLN1A, and ARFGEF2 genes. Polymicrogyria results from abnormal late cortical organization and is inconstantly associated with abnormal neuronal migration. Localized polymicrogyria has been associated with anatomo-specific deficits, including disorders of language and higher cognition. Polymicrogyria is genetically heterogeneous and only in a small minority of patients has a definite genetic cause been identified. Megalencephaly with normal cortex by imaging, megalencephaly with polymicrogyria, dysplastic megalencephaly (including hemimegalencephaly), and focal cortical dysplasia can all result from mutations of the same genes in the PI3K-AKT-mTOR pathway which are often postzygotic and can be limited to the dysplastic tissue in the less diffuse forms.

List of Abbreviations

a > p

Anterior > posterior


Bilateral frontoparietal PMG


Bilateral perisylvian PMG


Copy number variants




Isolated LIS




Malformations of cortical development


Miller-Dieker syndrome


Multiplex ligation-dependent probe amplification


Magnetic resonance imaging

p > a

Posterior > anterior




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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pediatric Neurology and Neurogenetics Unit and Laboratories, Neuroscience DepartmentA. Meyer Children’s Hospital – University of FlorenceFlorenceItaly

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