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

Epileptic Disord. 2022 Jun 1;24(3):572-576. doi: 10.1684/epd.2022.1417.


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.

Publication types

  • Case Reports

MeSH terms

  • Cerebellum
  • Child
  • Developmental Disabilities / genetics
  • Epilepsy* / genetics
  • Female
  • Humans
  • Intellectual Disability* / genetics
  • Mutation, Missense
  • Phenotype