PMG: Polymicrogyria BFPP: Bilateral frontoparietal PMG BPP: Bilateral perisylvian PMG CNV: copy number variants EEG: Electroencephalogram ILS: isolated LIS LIS: Lissencephaly MCD: Malformations of cortical development MLPA: Multiplex Ligation-dependent Probe Amplification MRI: Magnetic resonance imaging MDS: Miller-Dieker syndrome

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, 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 Renzo Guerrini and Elena Parrini Pediatric Neurology and Neurogenetics Unit and Laboratories, Neuroscience Department, A. Meyer Children‘s Hospital, University of Florence, Florence, Italy Malformations of Cortical Development (MCD): Genetic Aspects