Acute encephalopathy after head trauma in a patient with a RHOBTB2 mutation

Abstract

ObjectiveDe novo missense mutations in the RHOBTB2 gene have been described as causative for developmental and epileptic encephalopathy.MethodsThe clinical phenotype of this disorder includes early-onset epilepsy, severe intellectual disability, postnatal microcephaly, and movement disorder. Three RHOBTB2 patients have been described with acute encephalopathy and febrile epileptic status. All showed severe EEG abnormalities during this episode and abnormal MRI with hemisphere swelling or reduced diffusion in various brain regions.ResultsWe describe the episode of acute encephalopathy after head trauma in a 5-year-old RHOBTB2 patient. At admission, Glasgow coma scale score was E4M4V1. EEG was severely abnormal showing a noncontinuous pattern with slow activity without epileptic activity indicating severe encephalopathy. A second EEG on day 8 was still severely slowed and showed focal delta activity frontotemporal in both hemispheres. Gradually, he recovered, and on day 11, he had regained his normal reactivity, behavior, and mood. Two months after discharge, EEG showed further decrease in slow activity and increase in normal electroencephalographic activity. After discharge, parents noted that he showed more hyperkinetic movements compared to before this period of encephalopathy. Follow-up MRI showed an increment of hippocampal atrophy. In addition, we summarize the clinical characteristics of a second RHOBTB2 patient with increase of focal periventricular atrophy and development of hemiparesis after epileptic status.ConclusionsAcute encephalopathy in RHOBTB2 patients can also be triggered by head trauma.

RHOBTB2 p.Arg511Trp Mutation in Early Infantile Epileptic Encephalopathy-64: Review and Case Report

“…The clinical features of the 13 cases with RHOBTB2 variants are summarized in ►Table 1. [6][7][8] Epilepsy was present in all of the individuals having onset in the first 3 years of life (between the first week and the ninth month, in 11 individuals). Seizure types were variable and included focal, generalized tonic-clonic seizures, as well as febrile seizures, and 8 of the 13 experienced SE.…”

Genetic causes of acute encephalopathy in adults: beyond inherited metabolic and epileptic disorders

“…In the genetic subtype, the MRI changes show a slightly different distribution in the external capsules, claustrum, limbic structures, and temporal lobes [ 52 ]. Interestingly, mutations in SCN1A, SCN2A, and RHOBTB2 genes can similarly confer susceptibility to post viral necrotizing encephalopathy [ 55 ]. Further discussion of these conditions is beyond the scope of this review.…”

Developmental and epileptic encephalopathy related to a heterozygous variant of the RHOBTB2 gene: A case report from French Guiana

“…De novo missense variants in RHOBTB2 were recently reported (Clinvar, n.d. ; Belal et al, 2018 ; Knijnenburg et al, 2020 ; Straub et al, 2018 ; Zagaglia et al, 2021 ) in 28 individuals with a phenotype including epilepsy, moderate to severe intellectual disability that was sometimes associated with developmental regression or plateauing, postnatal microcephaly, and movement disorders. All of these variants cluster in or close to either the first or second BTB domain, at positions important for stabilizing interactions within the domain or for dimer formation as well as impaired degradation of RHOBTB2 by the proteasome.…”

“…Some patients had only late‐onset febrile seizures. At least five patients were reported to have acute encephalopathy and epileptic seizures triggered by hyperthermia or head trauma (Belal et al, 2018 ; Knijnenburg et al, 2020 ). The movement disorder appears characteristic, associating ataxia, dystonia and paroxysmal chorea‐like movements, and alternating hemiplegia of childhood (AHC).…”

“…In conclusion, we have identified a de novo variant of RHOBTB2 as a rare genetic cause of epileptic encephalopathy. Our case report clearly supports the conclusions of previous studies (Clinvar, n.d. ; Belal et al, 2018 ; Knijnenburg et al, 2020 ; Niu et al, 2021 ; Straub et al, 2018 ; Zagaglia et al, 2021 ), albeit with some specificities. However, how RHOBTB2 variants lead to epileptic encephalopathy remains unknown.…”