John Libbey Eurotext

Biallelic SZT2 variants in a child with developmental and epileptic encephalopathy Volume 22, numéro 4, August 2020


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1 Department of Pediatrics,
2 Education Center, Asahikawa Medical University, Asahikawa, Japan
3 Medical Genome Center, National Center for Child Health and Development, Tokyo, Japan
4 Department of Genome Medicine, National Center for Child Health and Development, Tokyo, Japan
* Correspondence: Ryosuke Tanaka Department of Pediatrics, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan

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.