First reported case of an inherited PACS2 pathogenic variant with variable expression

ABSTRACT

Neonatal epilepsy, cerebellar dysgenesis and facial dysmorphisms may be associated with de novo PACS2 missense pathogenic variants (EIEE 66) (OMIM #618067). Here, we report a toddler boy with neonatal-onset seizures, developmental delay with hypotonia, facial dysmorphisms and prominence of the cisterna magna, mild inferior vermian and cerebellar hypoplasia. A nextgeneration epilepsy gene panel revealed a known pathogenic PACS2 missense variant, p.Glu209Lys, that was inherited from his mildly affected mother. We describe the first PACS2 pathogenic variant to be inherited, expanding the clinical spectrum, associated with a mild phenotype in the mother and a more severe phenotype in her son, in keeping with previously reported descriptions.