Malformations of cortical development (MCD) are a heterogenous group of brain malformations including lissencephaly, heterotopia and polymicrogyria. The lissencephaly spectrum (including lissencephaly, pachygyria and subcortical band heterotopia) is a well-defined group of MCD with a strong monogenetic basis. Using current molecular techniques, a causative variant is detected in approximately 80% of individuals with lissencephaly. In a routine diagnostic setting, exome-based gene panels are most frequently used while whole exome sequencing (WES) and whole genome sequencing (WGS) are increasingly being implemented. Both techniques have their shortcomings including the detection of small copy number variants, the identification of pathogenic variants in non-coding regions as well as variant interpretation. The parallel use of quantitative RNA sequencing, measuring differences in RNA expression could be a possible solution for these shortcomings. The proposed research project will for the first time 1) evaluate the added value of WES/WGS combined with quantitative RNA sequencing for the identification of novel genes in individuals with lissencephaly, 2) identify the optimal sampling tissue for RNA sequencing in complex neurological phenotypes and 3) use RNA expression data to provide an evidence base for the current lissencephaly classification.