UBA5 ‐epileptic encephalopathy: new patient, a novel variant, and a review of epileptic phenotypes

Le résumé fourni par la source

Protein ufymilation is a post-translational modification implicated in the regulation of several cellular processes. Biallelic variants in UBA5 causing a functional alteration of its protein product have been associated with early-onset epileptic encephalopathy 44 (EIEE44), a rare disease for which 28 patients have been described in the literature at present. We here report on the clinical and detailed EEG phenotype of a novel patient affected by EIEE44. At 5 months of age, she presented with psychomotor delay, failure to thrive, and postural abnormalities. At 6 months of age, the EEG showed disorganization during both wakefulness and sleep, with numerous anomalies and the recording of epileptic myoclonus during falling asleep, in the absence of significant MRI correlates. Upon follow-up after 1 month, the findings were suggestive of epileptic spasms. Valproate was then introduced, and vigabatrin was later added due to the onset of cluster episodes. Excessive drowsiness required a slow titration of the pharmacological therapy. At 2 years of age, height and weight were still below the first centile. No more drowsiness was noted, but psychomotor delay and limb hypertonia persisted. The EEG remains disorganized during both wakefulness and sleep, with the presence of numerous interictal anomalies. We suggest UBA5 to be added to the genes that are routinely tested or analyzed when early-onset epileptic encephalopathy is suspected. In the event of a genetic diagnosis of EIEE44, patients' management could benefit from state-of-the-art clinical, prognostic, and therapeutic knowledge, which, in turn, would be further refined thanks to additional phenotypic reports.

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