Infantile‐onset myoclonic developmental and epileptic encephalopathy: A new RARS2 phenotype

Abstract

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KETASER01 protocol: What went right and what went wrong

“…This may be particularly true when SE occurs in an epileptic encephalopathy (EE), in which the underlying clinical conditions sometimes prevent assessment of the SE and a clear distinction between interictal and ictal discharges on EEG. [20][21][22] Myoclonic SE can also at times be difficult to diagnose, especially when myoclonias are subtle and parcellar, as in our patient n = 8. Awareness of this condition may justify the decision to exclude EE from future SE clinical trials or to build a specific protocol study, considering a prompt and more aggressive treatment in these disorders.…”

“…The development of SE may be insidious and long‐lasting, with seizures that occur and become drug‐resistant over a period of hours and days, in spite of the use of anti‐seizure medications. This may be particularly true when SE occurs in an epileptic encephalopathy (EE), in which the underlying clinical conditions sometimes prevent assessment of the SE and a clear distinction between interictal and ictal discharges on EEG 20–22 . Myoclonic SE can also at times be difficult to diagnose, especially when myoclonias are subtle and parcellar, as in our patient n = 8.…”

Severe neonatal onset neuroregression with paroxysmal dystonia and apnoea: Expanding the phenotypic and genotypic spectrum of CARS2‐related mitochondrial disease

“…Though most have striking pontocerebellar hypoplasia, 21 a recent report describes two older patients without clear MR imaging abnormalities. 22 Treatment refractory epilepsy, progressing to early death from three to 28 years of age, has been described in all reported cases of CARS2-related disease (Table 1). In contrast, the proband reported here underwent five EEG recordings over the course of his short life with capture of clinical events and showed no clear evidence of epileptiform activity.…”

“…Pathogenic variants in RARS2 , the gene encoding the mitochondrial tRNA synthetase for arginine, lead to a similar neuroregressive clinical phenotype. Though most have striking pontocerebellar hypoplasia, 21 a recent report describes two older patients without clear MR imaging abnormalities 22 . Treatment refractory epilepsy, progressing to early death from three to 28 years of age, has been described in all reported cases of CARS2 ‐related disease (Table 1).…”

A non-coding variant in the Kozak sequence of RARS2 strongly decreases protein levels and causes pontocerebellar hypoplasia

“…RARS2 protein is involved in the addition of arginine to tRNA, thus allowing translation of mitochondrial proteins. Splice site, nonsense, or missense variants on RARS2 gene have been reported in more than 50 cases, with PCH estimated to be present in half of them [ 18 – 23 ].…”