A de novo in-frame deletion of CASK gene causes early onset infantile spasms and supratentorial cerebral malformation in a female patient

Am J Med Genet A. 2018 Nov;176(11):2425-2429. doi: 10.1002/ajmg.a.40429. Epub 2018 Oct 5.

Abstract

We report a female patient with a novel, heterozygous, de novo in-frame deletion in the CASK gene (c.2179-2181 del GTA, p.Val727del) who presents with early onset infantile spasms, hypsarrhythmia on electroencephalogram (EEG), and frontal lobe abnormalities on brain magnetic resonance imaging (MRI) without microcephaly and pontocerebellar hypoplasia. This is the first case report of an in-frame deletion in the CASK gene causing early onset infantile spasms and supratentorial focal brain malformation on brain MRI in the literature. This is also the first report of a female with CASK-related disorder with hypsarrhythmia pattern on EEG. This report expands the clinical phenotypic spectrum in CASK-related disorders in female patients. A heterozygous de novo variant in RORA (c.88 C>G, p.Gln 30Glu) was reported in this patient as a variant of uncertain significance.

Keywords: CASK gene; infantile spasms; microcephaly and pontocerebellar hypoplasia; supratentorial brain malformation.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Age of Onset
  • Child, Preschool
  • Electroencephalography
  • Female
  • Guanylate Kinases / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Nervous System Malformations / complications*
  • Nervous System Malformations / diagnostic imaging
  • Nervous System Malformations / genetics*
  • Phenotype
  • Sequence Deletion / genetics*
  • Spasms, Infantile / complications*
  • Spasms, Infantile / diagnostic imaging
  • Spasms, Infantile / genetics*

Substances

  • CASK kinases
  • Guanylate Kinases