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Case Reports
. 2020 Oct;9(5):707-712.
doi: 10.21037/tp-20-110.

A term neonate with early myoclonic encephalopathy caused by RARS2 gene variants: a case report

Yan Xu  1 , Bing-Bing Wu  2 , Hui-Jun Wang  2 , Shui-Zhen Zhou  1 , Guo-Qiang Cheng  3 , Yuan-Feng Zhou  1
Affiliations
Case Reports

A term neonate with early myoclonic encephalopathy caused by RARS2 gene variants: a case report

Yan Xu et al. Transl Pediatr. 2020 Oct.

Abstract

The RARS2 gene encodes mitochondrial arginine-tRNA synthetase. Patients with variants of the RARS2 gene have pontocerebellar hypoplasia type 6 (PCH6), which is characterized by early onset seizures, progressive microcephaly, and developmental delay. PCH6 is a rare mitochondrial encephalopathy. To the best of our knowledge, the onset seizure type which the ictal video-electroencephalogram (VEEG) was compatible with early myoclonic encephalopathy (EME) has not been reported. Here we reported a term female neonate with EME caused by heterozygous variants of the RARS2 gene [NM_020320: exon10: c.773G>A (p. R258H) Maternal, NM_020320: exon4: c.282_285delAGAG Paternal]. Groan was the first symptom manifested, followed by metabolic disorders, and early marked cerebral atrophy. Metabolic disorders were corrected after feeding with extensively hydrolyzed protein formula. Seizures started at the 19th day of life. Interictal VEEG showed a suppression-burst (SB) pattern and ictal VEEG revealed myoclonic seizures that were compatible with early myoclonic encephalopathy (EME). She had frequent myoclonic seizures resistant to multi-antiepileptic drugs including phenobarbital, levetiracetam and oxcarbazepine, and soon developed into convulsive status epilepticus. At 7 months of age, she had severe developmental delay, and developed infantile spasms. Our case report expands the phenotypic spectrum of the PCH6, meanwhile, RARS2 should be considered be a causative gene in patients with EME.

Keywords: Mitochondrial arginyl-tRNA synthetase 2 (RARS2); case report; early myoclonic encephalopathy (EME).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-20-110). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
VEEG at DOL24. International 10–20 system modified for neonates, HHF: 70 Hz, Sensitivity 10 µV/mm. Interictal EEG showed a symmetric and synchronous SB pattern. Ictal EEG revealed frequent myoclonic seizures often coincided the burst phases. Arrow: myoclonic seizures. Electromyogram 1 (EMG1)/EMG2: distal left/right upper extremity muscles. EMG3/EMG4: distal left /right lower extremity muscles.
Figure 2
Figure 2
Brain MRI at DOL27 (axial T1-weighted imaging). (A,B) Marked supratentorial atrophy, obviously at the left side; significant small vessels in bilateral temporal region and hypomyelination in the posterior limb of internal capsule.
Figure 3
Figure 3
Image obtained on Sanger sequencing. A depicts a (G>A) variant in the RARS2 gene from the mother; B depicts a (c.282_285delAGAG) variant in the RARS2 gene from the father.
Figure 4
Figure 4
Timeline of this case. AEDs, antiepileptic drugs; MRI, magnetic resonance imaging; VEEG, video-electroencephalogram.
See this image and copyright information in PMC

References

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