Heterogenous genetic patterns in bilateral perisylvian polymicrogyria: insights from a Finnish family cohort

Abstract Bilateral perisylvian polymicrogyria is the most common form of regional polymicrogyria within malformations of cortical development, comprising 20% of all MCDs. BPP is characterized by excessive folding of the cerebral cortex and abnormal cortical layering. Notable clinical features include upper motoneuron dysfunction, dysarthria, and asymmetric quadriparesis. Cognitive impairment and epilepsy are frequently observed. To identify genetic variants underlying BPP in Finland, we examined 21 families using standard exome sequencing, complemented by optical genome mapping and/or deep exome sequencing. Pathogenic or likely pathogenic variants were identified in 5/21 (24%) of families, of which all were confirmed as de novo. These variants were identified in five genes, i.e., DDX23, NUS1, SCN3A, TUBA1A, and TUBB2B, with NUS1 and DDX23 being associated with BPP for the first time. In conclusion, our results confirm the previously reported genetic heterogeneity of BPP and underscore the necessity of more advanced methods to elucidate genetic background of BPP.