P 1151. A 19-Month-Old Boy with Mild Epileptic Encephalopathy and Mutation in the SZT2 Gene

Background: Already in early childhood, a multitude of different gene mutations can lead to a severe epileptic encephalopathy including mutations in the STZ2 gene discovered only in recent years. The phenotypic spectrum of patients with pathogenic mutations in the SZT2 gene is ranging from encephalopathy with severe developmental delay to mild mental retardation without epilepsy. Most patients are suffering also from muscular hypotonia, microcephaly, corpus callosum alterations, and facial dysmorphic features. Studies in animals suggest that the altered protein function leads to an inhibition of the maturation of axons and brain development. Furthermore, there is evidence that the SZT2 protein prevents oxidative toxicity of glutamate in neuronal cells.

Case Report: We report the first child of nonconsangious parents, born after uneventful pregnancy and birth. At the age of 11 months, seizures occurred characterized by twisting of the eyes, apnea with deep cyanoses, and reduction of SpO₂ as low as 20%. Up to 11 seizures a day were observed over a period of a month. Neurological examination revealed a truncal hypotonia, gross-motor developmental delay, a relative macrocephaly but no facial dysmorphic features. The EEG showed sharp waves in the right frontal regions of the brain. A cerebral magnetic resonance imaging (MRI) was reported as normal and chromosomal analysis revealed a normal karyotype. The CGH array was normal. As a next step, a diagnostic panel for the following genes associated with severe epileptic encephalopathy was requested: CDKL5, KCNQ2, SCN1A, SCN2A, SCN8A, STXBP1, and SZT2.

Two heterozygote mutations in the SZT2 gene were found: Chr1:43881653/43881655; NM_015284.3 c654_655del; p.(Asp220Profs*14) and Chr1: 43908001; NM_015284.3 c7765C>T; p(Arg2589Trp). One is a frameshift and the other a missense mutation of the SZT2 gene. Genetic testing of the parents is still pending.

The seizures are controlled with a combination of valproate and levetiracetam since the age of 12 months. At the age of 19 months, the boy is still suffering from gross-motor developmental delay. He is able to sit, crawl, and is able to walk along furniture. His cognitive development appears to be mildly delayed.

Conclusion: Only a few publications of individual cases with mutations in the SZT2 gene do exist. Normally, children do have a therapy-resistant epilepsy. Here, we report a child, whose seizure disorder could be controlled with two antiepileptic medications and who had no pathological MRI findings extending the spectrum of children with a SZT2 gene mutation.