Familial posterior predominant subcortical band heterotopia caused by a CEP85L missense mutation

Lissencephaly comprises a spectrum of cortical malformations caused by disruption of neuronal migration. The lissencephaly spectrum includes agyria defined as cortex lacking gyri with sulci >3cm apart, pachygyria defined as abnormally broad gyri with sulci 1.5-3cm apart, and subcortical band heterotopia (SBH) characterised by a band of heterotopic neurons beneath the cortex, separated by a thin layer of white matter. Lissencephaly has heterogeneous genetic aetiologies, including both single gene mutations (for example, LIS1 and DCX variants) and locus deletions (for example, 17p13.3 deletion causing Miller-Dieker syndrome). A systematic analysis of a large lissencephaly cohort, found a causative mutation in 81% of children, with pathogenic variants in LIS1, DCX, TUBA1A and DYNC1H1 accounting for 69% of all cases. Mutations in specific lissencephaly genes correlated with particular patterns of brain MRI abnormalities: DCX mutations were associated with anterior predominant lissencephaly and LIS1 mutations with posterior predominant lissencephaly. Most unsolved cases had posterior predominant lissencephaly. Heterozygous variants in the CEP85L gene were first identified as a cause of lissencephaly in 2020. Here we highlight the characteristic clinico-radiological CEP85L phenotype in an Irish family with parieto-occipital SBH and focal epilepsy.