RARS2 mutations cause early onset epileptic encephalopathy without ponto-cerebellar hypoplasia

Daniella Nishri, Hadassa Goldberg-Stern, Iris Noyman, Lubov Blumkin, Sara Kivity, Hirotomo Saitsu, Mitsuko Nakashima, Naomichi Matsumoto, Esther Leshinsky-Silver, Tally Lerman-Sagie, Dorit Lev

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Introduction Early onset epileptic encephalopathies (EOEEs) are a group of devastating diseases, manifesting in the first year of life with frequent seizures and/or prominent interictal epileptiform discharges on the electroencephalogram, developmental delay or regression and usually a poor prognosis. There are numerous causes for EOEEs making the diagnostic workup time consuming and costly. Methods We describe two siblings with fatal EOEE, profound global developmental delay and post-natal microcephaly that underwent extensive biochemical and metabolic workup in vain. Neuro-imaging disclosed non-specific progressive cerebral atrophy. Results Whole-exome sequencing (WES) disclosed compound heterozygous mutations in the gene encoding for mitochondrial arginyl-transfer RNA synthetase, RARS2. This gene has been previously described as the cause of pontocerebellar hypoplasia type 6. Conclusion We suggest that RARS2 gene mutations can cause a metabolic neurodegenerative disease manifesting primarily as EOEE with post-natal microcephaly, without the distinctive radiological features of pontocerebellar hypoplasia.

Original languageEnglish
Pages (from-to)412-417
Number of pages6
JournalEuropean Journal of Paediatric Neurology
Issue number3
StatePublished - 1 May 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 European Paediatric Neurology Society.


  • Epileptic encephalopathy
  • Mitochondrial
  • Pontocerebellar hypoplasia
  • RARS2


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