Biallelic SZT2 variants in a child with developmental and epileptic encephalopathy

Epileptic Disord. 2020 Aug 1;22(4):501-505. doi: 10.1684/epd.2020.1187.


Developmental and epileptic encephalopathy is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability, in which there is additional developmental impairment independent of epileptic activity. Biallelic variants of SZT2, a known seizure threshold regulator gene, have been linked to a wide spectrum of clinical features, ranging from severe intellectual disability with refractory seizures to mild intellectual disability without seizures. Here, we describe a child with developmental and epileptic encephalopathy whose genetic testing led to the identification of novel biallelic variants of SZT2, a paternally inherited c.2798C>T, p.(Ser933Phe) variant and a maternally inherited c.4549C>T, p.(Arg1517Trp) variant. Our patient showed common clinical and radiographic features among patients with SZT2-related encephalopathy. However, neonatal-onset seizures and suppression-burst EEG activity, not previously associated with SZT2-related encephalopathy, were observed in this case. Although the seizures were controlled with carbamazepine, the developmental consequences remained profound, suggesting that the developmental impairments might be attributed to a direct effect of the SZT2 variants rather than the epileptic activity. We propose that SZT2 variants should be regarded among those that are believed to cause neonatal-onset developmental and epileptic encephalopathy with a suppression-burst pattern on EEG.

Keywords: SZT2; developmental and epileptic encephalopathy; electroencephalogram; epilepsy; intellectual disability; suppression-burst.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / physiopathology
  • Electroencephalography
  • Epilepsy / diagnosis
  • Epilepsy / genetics*
  • Epilepsy / physiopathology
  • Female
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Nerve Tissue Proteins / genetics*


  • Nerve Tissue Proteins
  • SZT2 protein, human