Further characterization of CEP85L‐associated lissencephaly type 10: Report of a three‐generation family and review of the literature

Abstract

Lissencephaly type 10 is a recently reported condition characterized by posterior predominant abnormalities in gyration with associated seizures, developmental delays or intellectual disability. We report a boy who presented at 5 years of age with epilepsy and developmental delays. His family history was notable for epilepsy in two prior generations associated with variable developmental and cognitive impact. Exome sequencing identified a novel missense variant in CEP85L [NM_001042475.2; c.196A>G, p.(Thr66Ala)] which segregated in four affected family members across three generations. Brain imaging of the proband demonstrated a posterior lissencephaly pattern with pachygyria, while other affected family members demonstrated a similar subcortical band heterotopia. This report expands the phenotypic spectrum of this rare disorder by describing a novel variant in CEP85L in a family with variable clinical and neuroimaging findings.

Novel lissencephaly-associated NDEL1 variant reveals distinct roles of NDE1 and NDEL1 in nucleokinesis and human cortical malformations

“…Migrating neurons with pathogenic variants are more likely to arrest on the path to the CP, hence separating from those with WT alleles. In contrast, both posterior predominant SBH and pachygyria have been independently observed in patients resulting from apparently germline CEP85L variants [ 14 , 30 , 33 , 43 , 71 ]. It is possible that other genetic or environmental factors affecting neuronal migration also play a role in modulating the severity of the disease.…”