Missense variants in RHOBTB2 in a patient with developmental and epileptic encephalopathy and paroxysmal movement disorder

Background: Mutations in the RHOBTB2 are associated with developmental and epileptic encephalopathy-64 (DEE 64), which is characterized by epilepsy, developmental delay, intellectual disability, microcephaly, and paroxysmal movement disorders. RHOBTB2-related DEE was first described in 2018 and currently, only 21 patients have been reported in the literature. Paroxysmal movement disorders are uncommon features in other DEE. Here, we describe a case with RHOBTB2 variant presenting DEE with severe paroxysmal movement disorders. Case presentation: The girl was born at 40 gestational weeks without perinatal problems. There was no family history of developmental delay or neurological disorders. She had delayed milestones after birth. She had her first seizure at 8 years old with status epilepticus with fever and acute encephalopathy. Brain MRI was normal. EEG showed diffuse encephalopathy with focal sharp waves from the left frontal area. She had infrequent focal seizures and infrequent focal dystonia on her feet. Seizures were relatively well controlled with oxcarbazepine and levetiracetam. However, at 22 years old, after COVID-19 vaccination, she presented severe dystonia and tremor on her feet. It was not explained with extensive workup including brain MRI, spine MRI, EEG and, laboratory findings. Trial of levodopa or risperidone was not effective in her movement symptoms. With the NGS gene panel, de novo missense RHOBTB2 variant (c.1519C>T, p.Arg507Cys) was identified. Conclusion: Mutations in the RHOBTB2 are associated with DEE and paroxysmal movement disorders. Paroxysmal movement disorders could be difficult to control with conventional medication.